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Dietary Fat Influences Testosterone, Cholesterol, Aminopeptidase A, and Blood Pressure in Male Rats
... The reduction in SAFA in substitution by MUFA attenuates the increase in blood pressure (BP) [4]. These alterations, depending on the degree of fatty acid saturation, are related to changes in the systemic or local renin-angiotensin systems (RAS) [5][6][7][8][9][10]. The activation of the RAS participates in the development of MetS, heart failure [11], and pathophysiology of hypertension [4,7,[12][13][14][15][16][17][18][19][20][21][22][23][24][25]. ...
... [4,7,9]. Elevated plasma cholesterol levels are another important risk factor widely recognized for its relationship with angiotensin metabolism [4,5,7,10,12,72], with Mediterranean countries showing lower rates of heart disease than other countries due to the usual diet rich in olive oil [75]. ...
... HFDs alter the baroreceptor reflex [76], and the type of fatty acid that makes up the diet is capable of modulating the central [10,26,77] and local RAS regulatory APs [4,5,7,9,57]. Our results show that the VOO diet favored the stabilization of the RAS with respect to the Bch diet, by lowering the values of GluAP (mb) activities in the aorta, ArgAP (mb) in the ventricle and aorta, and CysAP (mb) in the atrium. ...
(1) Background: The replacement of diets high in saturated fat (SAFA) with monounsaturated fatty acids (MUFA) is associated with better cardiovascular function and is related to the modulation of the activity of the local renin–angiotensin system (RAS) and the collagenase activity of dipeptidyl peptidase IV (DPP-IV). The objective of the work was to verify the capacity of different types of dietary fat on the regulatory activities of RAS and DPP-IV. (2) Methods: Male Wistar rats were fed for 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or with butter (20%) plus cholesterol (0.1%) (Bch). The proteolytic activities were determined by fluorometric methods in the soluble (sol) and membrane-bound (mb) fractions of the left ventricle and atrium, aorta, and plasma samples. (3) Results: With the VOO diet, angiotensinase values were significantly lower than with the Bch diet in the aorta (GluAP and ArgAP (mb)), ventricle (ArgAP (mb)) and atrium (CysAP (sol)). Significant decreases in DPP-IV (mb) activity occurred with the Bch diet in the atrium and aorta. The VOO diet significantly reduced the activity of the cardiac damage marker LeuAP (mb) in the ventricle and aorta, except for LeuAP (sol) in the ventricle, which was reduced with the Bch diet. (4) Conclusions: The introduction into the diet of a source rich in MUFA would have a beneficial cardiovascular effect on RAS homeostasis and cardiovascular functional stability.
... On the other hand, the reduction of saturated fatty acids in substitution by other sources of mono-/poly-unsaturated fatty acids attenuated the development of hypertension. These alterations depending on the degree of saturation of the fatty acid could be related to changes in the systemic or local renin angiotensin systems (RAS) [14,15] including the kidneys, due to their direct association with the development of hypertension [16][17][18]. ...
... Different local RASs could be affected by changes in the degree of saturation of fat consumed in the diet. Within these local systems, angiotensin peptides are metabolized by various enzymes of the aminopeptidase (AP) family, also called angiotensinases, and previous results of our research group have shown that the activities of these peptidases are affected by the type of fatty acids consumed with the diet [5,14,25,26]. These APs are relevant in the control of blood pressure (BP) and renal function, participating in the regulation of the systemic and local RAS, but also like predictive renal injury biomarkers on the luminal surface of the renal tubule [27,28]. ...
... Among them, aspartyl-AP activities (AspAP; EC 3.4.11.21), responsible for the metabolism of Ang I to Ang 2-10; glutamyl-AP (GluAP or aminopeptidase A, APA; EC 3.4.11.7), metabolizes Ang II into Ang III; alanyl-AP (AlaAP or aminopeptidase M, APM; EC 3.4.11.2) and/or arginyl-AP (ArgAP or aminopeptidase B, APB; EC 3.4.11.6), responsible for the metabolism of Ang III to Ang IV and Ang 4-8; insulin-regulated AP (IRAP; 3.4.11.3), also called placental AP-leucyl (LAP), cystinyl-AP (CysAP), oxytokinase or vasopressinase, which as mentioned above, was identified as the binding site for the AT4 receptor Ang IV [29][30][31][32]. It has been suggested that the metabolizing activity of Ang II (GluAP) may be influenced by the composition of fatty acids in the diet and by the cholesterol content [5,14,15,33] directly or indirectly, and with an important role in the development of cardiovascular and kidney disorders. ...
High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.
... (B) Relative percentages of saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids in the oils used in the present study to enrich the different types of diets: Respectively (SAFA, MUFA, PUFA), for sesame- (15.7, 41, 43.4), sunflower-(12, 22.4, 60.7), fish- (12, 45.8, 41.6), olive-(13.2, 73.2, 8.9), 62,9.4), and coconut-oil (86.5, 5.8, 1.8) (Segarra et al., 2008). (C) Mean ± S.E.M. levels (n = 8) of AlaAP and CysAP activities (nmol/min/mg prot) obtained in frontal cortex, liver and plasma of male rats fed during 16 weeks with diets enriched with sesame-(S, charcoal), sunflower-(SF, rose), fish-(F, gray), olive-(O, cyan), Iberian lard-(L, magenta) and coconut-oil (C, brown). ...
... The type of fat in the diet modifies the profile of fatty acids and the levels of certain neuropeptidase activities in frontal cortex (Segarra et al., , 2019a as well as the levels of cholesterol in plasma (Segarra et al., 2008). In addition, the type of fat in the diet affects the correlation between some neuropeptidase activities and certain fatty acids in frontal cortex (Segarra et al., , 2019a. ...
... Forty eight adult male Wistar rats, weighing 200-250 g (aged 3-4 months) at the beginning of the study, were divided in six groups (n = 8 each), individually housed in metabolic cages and kept under standard environmental conditions. To ensure a full effect of the diets on experimental animals and based on the average length of the diet used in the literature, each group was fed during 16 weeks with isocaloric diets supplemented with 10% of the different oils studied: S, SF, F, O, L, and C (Segarra et al., 2008). At the end of the feeding period, the rats were weighed and their systolic blood pressure recorded by plethysmography (Segarra et al., 2008). ...
Insulin-regulated aminopeptidase (IRAP, cystinyl aminopeptidase, CysAP) and aminopeptidase M (alanyl aminopeptidase, AlaAP) are closely related enzymes involved in cognitive, metabolic, and cardiovascular functions. These functions may be modulated by the type of fat used in the diet. In order to analyze a possible coordinated response of both enzymes we determined simultaneously their activities in frontal cortex, liver, and plasma of adult male rats fed diets enriched with fats differing in their percentages of saturated, mono or polyunsaturated fatty acids such as sesame, sunflower, fish, olive, Iberian lard, and coconut. The systolic blood pressure, food intake, body and liver weight as well as glucose and total cholesterol levels in plasma were measured. The type of fat in the diet influences the enzymatic activities depending on the enzyme and its location. These results suggest cognitive improvement properties for diets with predominance of polyunsaturated fatty acids. Physiological parameters such as systolic blood pressure, food intake, and biochemical factors such as cholesterol and glucose in plasma were also modified depending on the type of diet, supporting beneficial properties for diets rich in mono and polyunsaturated fatty acids. Inter-tissue correlations between the analyzed parameters were also modified depending on the type of diet. If the type of fat used in the diet modifies the behavior and relationship between CysAP and AlaAP in and between frontal cortex, liver and plasma, the functions in which they are involved could also be modified.
... Plasma was isolated by centrifugation of blood samples for 10 min at 2000 g using heparin as an anticoagulant and stored at −20 °C 8 . Total plasma cholesterol was determined colorimetrically using kits supplied by Sigma (St Louis, MO, 352-50) 44 . HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . ...
... Total plasma cholesterol was determined colorimetrically using kits supplied by Sigma (St Louis, MO, 352-50) 44 . HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . LDL cholesterol fractions were calculated using Friedewald's formula 44 . ...
... HDL cholesterol precipitated with phosphotungstic acid was quantified with the same method 44 . LDL cholesterol fractions were calculated using Friedewald's formula 44 . NO levels in plasma and urine were analyzed as previously described 36 . ...
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.
... Local RASs could be altered by different degrees of saturation in dietary fat. Angiotensin peptides are metabolized by several angiotensinases, and we have previously demonstrated that those activities are affected by dietary fatty acids [5,29,30]. ...
... The relative amounts of angiotensines are regulated by the activity of several aminopeptidases, namely angiotensinases ( Figure 3A). It is known that these activities are modulated by dietary fat [5,29,30,54,81,82]. Previous results have demonstrated that liver angiotensinases are altered by the thyroid status [83] and obesity [84,85]. ...
High-fat diets (HFD) have been widely associated with an increased risk of metabolic disorders and overweight. However, a high intake of sources that are rich in monounsaturated fatty acids has been suggested as a dietary agent that is able to positively influence energy metabolism and vascular function. The main objective of this study was to analyze the role of dietary fats on hepatic peptidases activities and metabolic disorders. Three diets: standard (S), HFD supplemented with virgin olive oil (VOO), and HFD supplemented with butter plus cholesterol (Bch), were administered over six months to male Wistar rats. Plasma and liver samples were collected for clinical biochemistry and aminopeptidase activities (AP) analysis. The expression of inducible nitric oxide synthase (iNOS) was also determined by Western blot in liver samples. The diet supplement with VOO did not induce obesity, in contrast to the Bch group. Though the VOO diet increased the time that was needed to return to the basal levels of plasma glucose, the fasting insulin/glucose ratio and HOMA2-%B index (a homeostasis model index of insulin secretion and valuation of β-cell usefulness (% β-cell secretion)) were improved. An increase of hepatic membrane-bound dipeptidyl-peptidase 4 (DPP4) activity was found only in VOO rats, even if no differences in fasting plasma glucagon-like peptide 1 (GLP-1) were obtained. Both HFDs induced changes in hepatic pyroglutamyl-AP in the soluble fraction, but only the Bch diet increased the soluble tyrosyl-AP. Angiotensinase activities that are implicated in the metabolism of angiotensin II (AngII) to AngIV increased in the VOO diet, which was in agreement with the higher activity of insulin-regulated-AP (IRAP) in this group. Otherwise, the diet that was enriched with butter increased soluble gamma-glutamyl transferase (GGT) and Leucyl-AP, iNOS expression in the liver, and plasma NO. In summary, VOO increased the hepatic activity of AP that were related to glucose metabolism (DPP4, angiotensinases, and IRAP). However, the Bch diet increased activities that are implicated in the control of food intake (Tyrosine-AP), the index of hepatic damage (Leucine-AP and GGT), and the expression of hepatic iNOS and plasma NO. Taken together, these results support that the source of fat in the diet affects several peptidases activities in the liver, which could be related to alterations in feeding behavior and glucose metabolism.
... However, concomitant oral administration of α-tocopherol (antioxidant) and simvastatin (a mild cholesterol lowering agent) to male hypercholesterolemic rats induced an additional protective effect on the reduced male fertility [1]; oleouropein supplementation, a phenolic compound in virgin olive oil, increase testicular testosterone levels in rats fed a high-protein diet [20], and the administration of olive oil to hipercholesterolemic male rabbits recovered the loss of semen quality and sperm functionality [21]. Previous results from our laboratory have demonstrated a differential effect of several fat sources on plasma GluAP activity and testosterone levels in male Wistar rats, indicating the importance of dietary fat components [22]. In addition, it has been reported that extra virgin olive oil reduced the adverse effects of genetically modified soya been on the reproductive organs of adult male rats [23], and it has been suggested that an appropriate mixture of olive oil and soybean oils may improve the redox homeostasis and steroidogenic status in rat testis [24]. ...
... Since no significant differences were found in these parameters between the VOO group and the S one, these effects seem to depend on the fat source. In this way, previous results have demonstrated that the dietary fat source and the changes in plasma lipid levels are related to testosterone synthesis [22] and an impaired testicular function, suggesting that hypercholesterolemia is an independent risk factor for testicular dysfunction [25]. In the present research, we found an increase in body weight and plasma lipids (total triglycerides and cholesterol) of animals fed the Bch diet when compared with the S diet, but no significant differences were found between the S and VOO groups. ...
The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). At the end of the experimental period, plasma lipid profiled (total triglycerides, total cholesterol and cholesterol fractions (HDL, LDL and VDL)) were measured. Enzymatic activities were determined by fluorimetric methods in soluble (sol) and membrane-bound (mb) fractions of testicular tissue using arylamide derivatives as substrates. Results indicated an increase in plasmatic triglycerides, total cholesterol, LDL and VLDL in Bch. A significant increase of mb GluAP and GGT activities was also found in this diet in comparison with the other two diets. Furthermore, significant and positive correlations were established between these activities and plasma triglycerides and/or total cholesterol. These results support a role for testicular GluAP and GGT activities in the effects of saturated fat (Western diet) on testicular functions. In contrast, VOO increased sol DPP IV activity in comparison with the other two diets, which support a role for this activity in the effects of monounsaturated fat (Mediterranean diet) on testicular function. The present results strongly support the influence of fatty acids and cholesterol on testicular GluAP and GGT activities and also provide support that the reported beneficial influence of the Mediterranean diet in male fertility may be mediated in part by an increase of testicular sol DPP IV activity.
... Rats given a regular diet enhanced with 25% sunflower oil had testosterone levels that were similar to those of rats given a normal diet without sunflower oil (Control). This is similar to another study by Segarra et al., (2008). In that study, the animals' diets were supplemented with 10% of the oils used. ...
Male reproductive processes are impacted by edible fats. The present work studied the effect of the consumption of a sunflower-enriched diet on sperm variables and reproductive hormones in male rats. A total of twenty male Wistar rats were used in this study. The Control group received the regular rat chow while the Treated group received the regular rat chow supplemented with 25% linoleic sunflower oil. After 28 days sperm variables, and reproductive hormones were assessed. There was no significant difference in the serum testosterone and prolactin levels in the group fed sunflower-enriched diet compared to the control group. The serum LDH and the seminal vesicle fructose levels were significantly increased in the animals fed sunflower enriched diet compared to the control animals. The sperm count and sperm motility levels were significantly higher in the rats fed sunflower enriched diet compared to the control rats. The current findings imply that while 25% linoleic sunflower oil might increase sperm characteristics, it might not have the same effect on testosterone levels.
... It is well established that the content of monoamines, particularly dopamine, is asymmetrically distributed in the brain and that a unilateral alteration of this distribution is part of the pathogenesis of Parkinson's disease in which not only motor alterations appear but also it is accompanied by depression and autonomic disturbances [33]. Certainly, the use of a polyunsaturate's enriched diet, compared to other diets, significantly modifies the content of fatty acids in the frontal cortex, especially increasing n3 PUFA [52]. Furthermore, it has been described that alterations in the n3 PUFA content in the diet are associated with alterations in the bilateral cerebral behavior possibly responsible for cognitive disorders [53]. ...
Although at present depression is one of the most disabling disorders in our social environment, the understanding of its pathogenesis and the resources for its treatment are still unsatisfactory. The importance of brain asymmetry in the pathogenesis of disorders in brain function, including mood disorders such as depression, is a highly unexplored, sometimes underrated, and even ignored topic. It is important to note that the basal and pathological functional lateralization must have an underlying neurochemical substrate. It is also necessary to indicate that the brain asymmetry extends to a neurovisceral integration whose behavior may also be lateralized. One of the most studied axis from the functional point of view is the brain-heart connection, in whose operation there are observations that suggest an asymmetric behavior in basal conditions that is modified by central and peripheral changes, as well as by pharmacological treatments. There are evidences that connect cardiovascular function, neurochemical asymmetries, and depression. A deep understanding of the bilateral behavior of the brain following pathophysiological changes in blood pressure as well as pharmacologically induced, can provide us with therapeutic suggestions for the treatment of depression. In this article, we analyze remarkable results of some representative selected contributions, with which we discuss our proposal on the relationship between hypertension, depression and neurochemical asymmetry.
... Three groups (n=8 each) of normal adult male Wistar rats (six-week-old, weighing 200-250 g, kept at room temperature of 22 ± 2ºC, with a relative humidity of 50-60% and a photoperiod of 12/12 h light/dark cycle) were individually housed in metabolic cages. Each group was fed during 16 weeks with an isocaloric diet supplemented with 10% of the oil under investigation: fish oil (F), olive oil (O) or coconut oil (C) (Segarra et al. 2008). Body weight (g) and food intake (g/day) were monitored throughout all the experimental period. ...
Objective. Enkephalins are neuropeptides involved in functions such as pain modulation and/ or cognitive processes. It has been reported that dietary fat modifies enkephalins in the brain. Since enkephalins are hydrolyzed by enkephalinases, the study of the influence of dietary fats, differing in their degree of saturation, on brain fatty acids content and enkephalinase activity is important to understand its regulatory role on neuropeptides under different type of diets.
Methods. We analyzed enkephalinase activity, assayed with alanine-β-naphthylamide as sub-strate, in frontal cortex of adult male rats fed diets supplemented with fish oil, olive oil or coconut oil, which markedly differed in the saturation of their fatty acids.
Results. Rats fed a diet enriched with coconut oil had lower soluble enkephalinase activity than the group fed olive oil (p<0.01) and fish oil (p<0.05) whereas rats fed a diet enriched with fish oil had lower membrane-bound enkephalinase activity than the group fed with olive (p<0.001) or coconut oil (p<0.05). Significant negative correlations were observed between certain fatty acids and enkephalinase activities in the groups fed with olive and coconut oils. No correlations were observed in the group fed with fish oil.
Conclusions. Dietary fat modifies enkephalinase activity in the frontal cortex depending on the degree of saturation of the used oil. It is postulated that the functions, in which enkephalins are involved, such as pain modulation or cognitive functions, may also be affected according to the type of oil used in the diet.
... Finally they were sacrificed by perfusing them through the same ventricle with saline solution [12]. Insulin, fasting glucose, triglycerides, total cholesterol, and HDL were measured as previously reported [12,22,23]. Leptin and ghrelin concentrations in plasma were also determined as previously reported [12,24]. ...
Extra virgin olive oil (EVOO) has been reported to have a distinct influence on gut microbiota in comparison to other fats, with its physiological benefits widely studied. However, a large proportion of the population consumes olive oil after a depurative process that not only mellows its taste, but also deprives it of polyphenols and other minority components. In this study, we compare the influence on the intestinal microbiota of a diet high in this refined olive oil (ROO) with other fat-enriched diets. Swiss Webster mice were fed standard or a high-fat diet enriched with EVOO, ROO, or butter (BT). Physiological parameters were also evaluated. At the end of the feeding period, DNA was extracted from feces and the 16S rRNA was pyrosequenced. The group fed ROO behaved differently to the EVOO group in half the families with statistically significant differences among the diets, with higher comparative levels in three families—Desulfovibrionaceae, Spiroplasmataceae, and Helicobacteraceae—correlating with total cholesterol. These results are again indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, but also support the possibility that polyphenols and minor components of EVOO are involved in some of the proposed effects of this fat through the modulation of the intestinal microbiota
... Plasma was isolated by centrifugation of blood samples for 10 min at 2000 g, using heparin as anticoagulant, and stored at-20˚C. In plasma samples, insulin, fasting glucose, triglycerides, total cholesterol and HDL were determined as previously [49,50]. Plasma concentrations of leptin and ghrelin, were measured in a multianalyte profiling by using the Luminex-100 system and the XY Platform [51]. ...
The type of fat in the diet determinates the characteristics of gut microbiota, exerting a major role in the development of metabolic syndrome. We hypothesize that a diet enriched with extra virgin olive oil (EVOO) has a distinctive effect on the intestinal microbiome in comparison with an enriched butter diet (BT) and this effect is related to the physiological benefits exerted by EVOO. Swiss Webster mice were fed standard (SD) or two high fat diets enriched with EVOO or butter. Hormonal, physiological and metabolic parameters were evaluated. At the end of the feeding period, DNA was extracted from faeces and the 16S rRNA genes were pyrosequenced. Among the main significant differences found, BT triggered the highest values of systolic blood pressure, correlating positively with the percentage of Desulfovibrio sequences in faeces, which in turn showed significantly higher values in BT than in EVOO. EVOO had the lowest values of plasmatic insulin, correlating inversely with Desulfovibrio, and had the lowest plasmatic values of leptin which correlated inversely with Sutterellaceae, Marispirillum and Mucilaginibacter dageonensis, the three showing significantly higher percentages in EVOO. The lowest total cholesterol levels in plasma were detected in SD, correlating positively with Prevotella and Fusicatenibacter, both taxa with significantly greater presence in SD. These results may be indicative of a link between specific diets, certain physiological parameters and the prevalence of some taxa, supporting the possibility that in some of the proposed effects of virgin olive oil the modulation of intestinal microbiota could be involved.
... Th ese changes may account for alterations in renal function during thyroid disorders . However, we have recently hypothesized that aminopeptidase activities are infl uenced in part by the biochemical environment created by the fl uctuating levels of factors such as cholesterol and steroids, especially testosterone, in the internal milieu (Martinez et al. 1998;Ramirez et al. 2008;Segarra et al. 2008). Alterations in serum cholesterol (Sauter et al. 1997) and testosterone levels (Bruni et al. 1975) are well documented in hypothyroidism and hyperthyroidism. ...
Thyroid disorders may affect blood pressure and renal function modifying factors of the plasmatic and kidney renin-angiotensin system such as aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We investigated the expression of AP A in the kidney, as well as its enzymatic activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male rats.
Hyperthyroidism was induced by daily subcutaneous injections of tetraiodothyronine. Hypothyroid rats were obtained by administration of methimazole in drinking water. Expression of AP A was determined by Western blot analysis. Plasma AP A activity was measured fluorometrically using glutamyl-β-naphthylamide as substrate.
While hyperthyroid rats exhibited lower levels of plasma AP A activity than controls, the kidney of hyperthyroid animals expressed significantly higher AP A than controls and hypothyroid animals.
A discrepancy between the high expression of AP A in kidney of hyperthyroid rats and the low activity of AP A measured in plasma and kidney of hyperthyroid animals was found. The posttranslational influence of environmental biochemical factors may be in part responsible for that divergence.
... ▼ Animals, diets, and collection of tissue samples 3 groups of adult male Wistar rats (200 -250 g, n = 8 in each group) were fed for 16 weeks with isocaloric diets. Each diet was supplemented with 10 % of the oil under investigation: fi sh oil, olive oil, or coconut oil [8] . At the end of the feeding period, rat brains were perfused with saline in light conditions (between 9:00 AM and 12:00 noon) through the left cardiac ventricle under equithensin anesthesia (2 ml / kg body weight) (equithensin contained: 42.5 g / l chloral hydrate dissolved in 19.76 ml ethanol, 9.72 g / nembutal ® , 0.396 l / l propylenglycol, and 21.3 g / l magnesium sulfate in distilled water), quickly removed and cooled in dry ice. ...
In order to study the interaction between the renin-angiotensin system (RAS) and nitric oxide (NO), we analyzed the activity of aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP), and cystinylaminopeptidase (CysAP) enzymes involved in the RAS cascade, in the hypothalamus, and plasma of normotensive adult male rats after the inhibition of NO production with the NO synthase inhibitor L-NAME (L-N (G)-nitroarginine methyl ester). L-NAME treatment produced a significant increase of systolic blood pressure (SBP). In plasma, while GluAP activity decreased significantly, suggesting a lower Ang III formation, the other aminopeptidases did not change after L-NAME treatment. In hypothalamus, the activities of AspAP and CysAP were not affected after L-NAME treatment. In contrast, GluAP and AlaAP increased significantly. These results suggested mainly a higher formation of Ang III, but also higher levels of Ang IV in the hypothalamus of L-NAME treated rats. Both peptides have hypertensive properties at central level. On the contrary, Ang III may counteract the hypertensive action of Ang II at the periphery. Therefore, the increased SBP in L-NAME treated rats may be due in part to the increased activity of GluAP and AlaAP in hypothalamus and to a decreased activity of GluAP in plasma.
... The molecular composition of each lipoprotein class has been comprehensively explored since the 1950s [1, 2] primarily by gasliquid chromatography and gas chromatography-mass spectrometry. New technologies, such as electrospray ionisa tion tandem mass spectrometry [3][4][5]and top-down lipidomics [6], have provided much deeper insight into the metabolism and clinical significance of hundreds of lipid species and, consequently, into pathophysiology of obesity, diabetes and arterial hypertension [7][8][9]. The positive correlation of plasmalogen levels with HDL (particularly apolipoprotein A-I), and their reduction with aging in patients with significant coronary stenosis and impaired glucose tolerance, have suggested beneficial functions of these antioxidant phospholipids [10, 11]. ...
Lipid apheresis is an efficient method for reducing cholesterol and triglyceride serum levels, but its effect on other lipid species has not been investigated. This study explored the effect of LDL apheresis on the serum lipidome in hyperlipidemic patients with cardiovascular complications. Lipid analysis was performed before and immediately after a single apheresis procedure in serum samples of six patients treated with different apheresis methods. Conventional lipid parameters (TC, LDL-C, HDL-C, TG) were determined by standard enzymatic methods. Phosphatidylcholines (PC), sphingomyelins (SM), phosphatidylethanolamines (PE), PE-based plasmalogens (PE_pl), lysophosphatidylcholines (LPC), ceramides (Cer), free cholesterol (FC) and cholesterol ester (CE) were detected with electrospray ionization tandem mass spectrometry. LDL apheresis induced a mean reduction of LDL-C by 68% and of HDL-C by 14%, respectively. CE, FC, SM, and Cer revealed an apheresis-induced decrease of about 47%, which was not statistically different from LDL-C reduction. In contrast, the decline of PC (31%), LPC (26%), PE (2%), and PE_pl (37%) after apheresis was significantly lower in comparison to LDL-C reduction, but not statistically different from HDL-C decrease. While the group of PC-species declined uniformly during apheresis, changes in particular LPC-, Cer-, and SM-species revealed significant differences, reflecting their differential distribution in lipoprotein particles and blood cells. We conclude that the acute effect of lipid apheresis on serum lipidome could be predominantly attributed to lipoprotein changes, while blood cell damages during this procedure caused additional, less pronounced changes. The importance of specific changes in particular lipid species remains to be established.
Male infertility has demonstrated to be a global health problem during last years. In this context, environmental contaminants and lifestyle mainly diet play an important role at the same time that provides an opportunity to develop new prevention strategies.
It is well stablished that diet rich in raw vegetables and fruit, similar to Mediterranean diet, could play a beneficial effect on spermatogenesis and reproductive function related to a high intake of antioxidants. In fact, the main cause of infertility in men is due to direct damage of reactive oxygen species at the nucleus and mitochondria DNA, and the lipid peroxidation in the membrane of the sperm.
On the other hand, Western diet has demonstrated to exert a negative impact on male fertility, as it is usually rich in saturated fatty acids and cholesterol. The changes in plasmatic lipid profile and the increase of cholesterol correlate with less sperm functionality.
Virgin olive oil, the major lipid source in the Mediterranean diet, provide a high amount of antioxidant, mainly polyphenols and others minors components, together a beneficial lipid composition, characterized by the contribution of monounsaturated fatty acids. Besides that, compared with others dietary fats, virgin olive oil presents a particular effect on several peptidases activities in testis, and these results seem to be related to changes in plasma lipid profile. Changes in angiotensinase activities in testis are able to modulate local renin–angiotensin system, with relevant functions in male fertility.
High-fat diets are associated with the development of cardiovascular diseases. The efficacy of the current strategies of treatment is still not entirely satisfactory, and new approaches are being considered. To analyze the beneficial effects of extra virgin olive oil as a major component of the Mediterranean diet, we studied systolic blood pressure and angiotensinase activities, since this enzyme is involved in the metabolism of angiotensins, in the kidney of hypertensive rats fed during 12 weeks with a diet enriched with extra virgin olive oil compared with a standard diet. As a reflex of oxidative stress, 8-isoprostanes and nitric oxide were quantified in urine. Results demonstrated a progressive increase in systolic blood pressure until the end of the feeding period in both groups. However, this increase was delayed in the extra virgin olive oil group until week six, with the systolic blood pressure being always lower in this group. Nitric oxide and 8-isoprostanes were lower in the extra virgin olive oil group. While we can deduce a higher formation of angiotensin 2-10 in the renal cortex, a higher availability of angiotensin II may be presumed in the renal medulla of animals fed an extra virgin olive oil diet than in animals fed a standard diet. Our results support the beneficial influence of extra virgin olive oil on cardiovascular function and suggest that the Mediterranean diet may be beneficial in itself but it may also be an effective tool in the treatment of hypertension.
The kind of fat in the diet modifies the profile of fatty acids in brain and also affects aminopeptidase activities in tissues. Although modifications in brain fatty acids, neurotransmitters, or enzymes due to dietary fat composition have been reported, no direct relationship has yet been described between specific brain fatty acid changes and neuropeptide metabolism following the fat composition of the diet. We investigated the lipid profile and some neuropeptidase activities in the frontal cortex of adult male rats after a period in which diets were supplemented with fatty acids differing in their degrees of saturation such as fish oil (rich in polyunsaturated fatty acids, PUFAs), olive oil (rich in monounsaturated fatty acids, MUFAs), and coconut oil (rich in saturated fatty acids, SAFAs). It is observed that the diet composition affects fatty acid distribution in the brain. Although there is no change of global aminopeptidase/neuropeptidase, their activities in the brain correlate positively or negatively with the dietary fat composition. It is hypothesized that fatty acid in the diet modifies membrane fluidity, peptidases tertiary structure, and therefore, the availability and function of neuropeptides. The present results support the notion that cognitive functions may be modulated depending on the type of fat used in the diet.
In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4.29 (SD 0.51), 5.30 (SD 0.67) and 5.58 (SD 0.76) mmol/l respectively, n 12) and HDL-cholesterol (3.31 (SD 0.50), 3.91 (SD 0.12) and 3.97 (SD 0.43) mmol/l) and these concentrations were significantly higher (P < 0.05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1.01 (SD 0.59), 1.56 (SD 0.65) and 2.75 (SD 1.03) mmol/l) and were significantly higher (P < 0.05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3 was significantly higher (P < 0.05) in the hamsters fed with maize oil (810 (SD 100) ng HDL3 protein/mg membrane protein, n 4) compared with those fed on palm oil (655 (SD 56) ng/mg), whereas the olive-oil group had intermediate values (674 (SD 26) ng/mg). The affinity of HDL3 for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC 3.1.1.3) activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm-oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes.
More than a century of research on the reninangiotensin system (RAS) has uncovered the widespread involvement of angiotensin II (Ang II) in the pathophysiology of cardiovascular diseases. A number of outcomes-based mega trials utilising hard clinical endpoints have revealed beneficial effects of angiotensin receptor antagonists (AIIAs/ARBs) in patients with hypertension, heart failure, diabetic nephropathy, and post-myocardial infarction (MI). The results of these studies not only emphasise the importance of Ang II in the pathophysiology of these diseases but have provided the basis for an evidence-based approach for the use of AIIAs in clinical practice. It is hoped that the next 100 years of research into the RAS will uncover hitherto unimaginable therapeutic opportunities.
We have analyzed the fatty acid composition of subcutaneous fat in the Iberian pork feed with acorns using gas chromatography. We have found a 59.1% content in oleic acid (18:1) and 62% of total monounsaturated fatty acids. This figures statistically does differs from the data about fat composition in pig taken from others food composition sources. We conclude that Iberian pork feed with acorns have a very high content in monounsaturated fatty acids and can no be considered as harmful as other animals fats.
The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n-6 (PUFA n-6); and polyunsaturated n-6/n-3, (PUFA n-3)]. Each diet period lasted 5 weeks. There were no differences in 24-h 2,3-dinor-6- keto-prostaglandin F1 alpha excretion among dietary periods. A significant effect was noted regarding the excretion of 11-dehydro-thromboxane B2 (P < 0.0001). During the PUFA n-6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 mumolL-1) and collagen (2 mgL-1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.
We studied the possible existence of physiological sex differences in serum aminopeptidase activities in mice, by evaluating the effect of gonadectomy and the in vitro response to the presence in the medium of cholesterol or steroid hormones. Alanyl- and glutamyl-aminopeptidase activities were measured in sera from male, female, orchiectomized and ovariectomized mice, incubated with substrate solutions, and compared with the same groups of serum incubated with substrate solutions including cholesterol, 17-beta-estradiol, testosterone, progesterone or hydrocortisone. Our results demonstrated highly significant sex differences, and an influence of cholesterol and steroid hormones on aminopeptidase activity. Depending on the nature of the aminopeptidase, these enzymes responded in different ways to the presence of these substances and also responded differently to gonadectomy. For alanyl-aminopeptidase activity, but not for glutamyl-aminopeptidase activity, there was a clear difference in response between males and females to incubation of the serum with steroid hormones.
Valsartan, a selective antagonist of angiotensin II at the AT(1) receptor subtype, is an efficacious, orally active, blood pressure-lowering agent used in hypertensive patients. Given that aminopeptidases (APs) play a major role in the metabolism of local peptides involved in blood pressure control, studying them helped us to understand cardiovascular control. We studied the effect of valsartan on angiotensin II- (GluAP) and vasopressin- (CysAP) degrading activities in the kidney in the rat model of renovascular hypertension, Goldblatt two-kidney one-clip. GluAP and CysAP in renal cortex and medulla exhibited different responses to hypertension and valsartan treatment. In the renal cortex, GluAP decreased in clipped and non-clipped kidneys of hypertensive animals. However, while hypertension did not affect GluAP in the clipped kidney medulla, the non-clipped kidney exhibited an increase in soluble and a decrease in membrane-bound activity. Valsartan decreased soluble GluAP in the medulla of normotensive and hypertensive animals. In the renal cortex, CysAP activity was mainly downregulated following hypertension. Valsartan decreased soluble CysAP activity in sham-operated, but not in hypertensive animals. The renal medulla showed a significant valsartan-related decreased activity in clipped and non-clipped kidneys of both sham-operated and hypertensive animals. These results suggest a functional relationship between the AT(1) receptor and vasopressin-degrading activity.
The autocrine/paracrine control mechanisms of local factors, such as the renin-angiotensin system and the thyrotropin-releasing hormone (TRH), seem to play a relevant role in testicular physiology. It has been proposed that dietary fat composition influences male reproductive function modifying the cholesterol-phospholipid composition of testicular plasma membranes. Modifications in the composition and physical properties of the membranes may lead to alterations in the activities of membrane-bound (M-B) enzymes. We have previously demonstrated that cholesterol and steroid hormones affect aminopeptidase (AP) activities. Dietary fatty acids with different degrees of saturation modified AP activities in the serum of mice and an olive oil supplemented diet influenced the AP activities in the testes of mice. We hypothesized that the modification of dietary fat composition may affect angiotensin- [glutamyl-AP (GluAP), aspartyl-AP (AspAP)] and TRH- [pyroglutamyl-AP (pGluAP)] degrading activities in the testis. In this study, we investigated the effect of diets supplemented with sunflower oil (SFO), fish oil (FO), olive oil (OO), lard (L) or coconut oil (CO) on soluble (Sol) and M-B GluAP, AspAP and pGluAP in mice testis, using arylamides as substrates. Sol GluAP activity did not show differences among groups. However, Sol AspAP and Sol pGluAP progressively decreased with the degree of saturation of the fatty acid used in the diet. In contrast, M-B GluAP progressively increased with the degree of saturation of the fatty acid used in the diet. For M-B AspAP activity, mice fed diets containing FO showed significantly higher levels than those fed diets containing SFO, OO and L but not those containing CO. For M-B pGluAP activity, the highest levels were observed for mice fed diets containing FO and OO. The present data suggest that the type of fat used in the diet may influence the autocrine/paracrine functions of locally synthesized angiotensin peptides and TRH in the testis, and consequently may be important in male reproductive functions.
The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca2+]i, and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.
Epidemiologic data from the Framingham Study provide insights into the population burden of heart failure (CHF), its prognosis and modifiable risk factors that promote it. In the general population CHF is chiefly the end stage of hypertensive, coronary and valvular cardiovascular disease. It is a major and growing problem in most affluent countries because of aging populations of increased size, and the prolongation of the lives of cardiac patients by modern therapy. Once clinically manifest, CHF, despite recent innovations in therapy, carries an unacceptably high mortality rate. In the Framingham Study, median survival is only 1.7 y for men and 3.2 y for women, with only 25% of men and 38% of women surviving 5 y. This is a mortality rate 4-8 times that of the general population of the same age. This poor outlook is observed for all etiologies of CHF and sudden death is a prominent feature of the mortality. Based on population attributable risks, hypertension has the greatest impact, accounting for 39% of CHF events in men and 59% in women. Despite its much lower prevalence in the population (3-10%) myocardial infarction also has a high attributable risk in men (34%) and women (13%). Valvular heart disease only accounted for 7-8% of CHF. Hypertension increased the age and risk factor adjusted hazard of CHF 2-fold in men and 3-fold in women, with a greater impact of the systolic than diastolic blood pressure. Diabetes increased CHF risk 2-8 fold with risk ratios twice as large in women as men. About 19% of CHF cases have diabetes. It accounted for 6-12% of the CHF in the Framingham Study cohort. Dyslipidemia characterized by a high total/HDL cholesterol ratio, but not the total cholesterol alone was a risk factor for CHF. An enlarged heart on X-Ray, ECG-LVH, a reduced vital capacity and rapid heart rate usually signified deteriorating cardiac function. CHF risk associated with ECG-LVH was independent of X-Ray cardiomegaly but risk was further augmented when both coexist. Echocardiographic left ventricular hypertrophy signifies a high risk of CHF proportional to the degree of increase in left ventricular mass without a critical value that delineates compensatory from pathological hypertrophy. Risk of CHF in persons predisposed by hypertension, diabetes or cardiac conditions varies over a 10-fold range depending on the aforementioned modifiable risk factors and indicators of deteriorating left ventricular function. Using multivariate risk formulations it is possible to identify 20% of the population from which 70% of the CHF will evolve. Those in the upper quintile of multivariate risk are good candidates for echocardiographic testing to delineate those needing aggressive preventive measures to delay the onset of CHF. Therapy of CHF must begin with treatment of presymptomatic left ventricular dysfunction to reverse the dysfunctional maladaptive changes.
The action of testosterone on the 45Ca2+ uptake and insulin secretion was studied in short-term experiments using isolated pancreatic islets of Langerhans. Testosterone (1 microM) stimulated 45Ca2+ uptake within 60 seconds of incubation on similar proportion than tolbutamide. Also, the hormone rapidly increased insulin release (34%; 180 seconds) on the presence of non-stimulatory concentrations of glucose (3 mM). Impermeant testosterone-BSA significantly stimulated the secretion of insulin to a lower percentage (10%). The action of the hormone is specific--neither 17beta-E2 nor progesterone stimulated insulin secretion in the presence of 3 mM glucose. The action of testosterone on insulin secretion was dose-dependent, and at rat plasma physiological concentrations (25 nM), stimulus was 17% (p < 0.05). In conclusion, in isolated pancreatic islets experiments, physiological concentration of testosterone rapidly stimulate insulin secretion and 45Ca2+ uptake through a membrane bound mechanism.
Thyroid disorders affect renal function, which involves changes in local renin angiotensin system (RAS). Angiotensin peptide levels in the tissue are regulated by the activity of several aminopeptidases (AP) known as angiotensinases. The nature and consequences of the thyroid-induced RAS changes are not completely understood. We investigated the relationship between thyroid status (hyper- and hypothyroidism) and several kidney AP actions involved in RAS control. We have determined fluorometrically soluble (SOL) and membrane-bound (M-B) alanylaminopeptidase (AlaAP), glutamylaminopeptidase (GluAP) and aspartylaminopeptidase (AspAP) activity using naphthylamide derivatives as substrates. Sprague-Dawley rats were divided into three groups--control, hyperthyroid, and hypothyroid. Hyperthyroidism was induced by daily subcutaneous injection of L-thyroxin (300 microg/kg/day). Hypothyroidism was induced by continuous administration of methimazole (0.03%) in drinking water. Hypothyroid animals demonstrated a significant increase in SOL and M-B GluAP activity in renal cortex and a decrease in M-B AlaAP compared to euthyroid rats. This result may suggest higher Ang III availability. In hyperthyroid animals, M-B AlaAP and M-B AspAP activity increased significantly, which may suggest increased Ang III to Ang IV metabolism and greater formation of Ang 2-10, respectively. In contrast, no differences were observed between euthyroid and hypothyroid animals for SOL and M-B AP activity in renal medulla. However, hyperthyroid animals demonstrated a significant decrease in SOL and M-B GluAP activity compared to euthyroid rats, which may suggest a greater availability of Ang II in renal medulla. Alterations in angiotensin metabolism may, in part, account for some changes in renal function during thyroid disorders.
To examine the relationship between serum levels of inflammatory cytokines and testosterone in men with stable coronary artery disease (CAD). Evidence supports a beneficial effect of testosterone upon objective measures of myocardial ischaemia in men with CAD, and in animal models of atherosclerosis. Inflammatory cytokines are involved in many stages of the atherosclerotic process, however, the effect of testosterone upon inflammatory cytokines within the cardiovascular system is largely unknown.
Serum was collected from 69 men (59+/-1 years) having >75% occlusion of 1, 2, or 3 coronary arteries. Levels of total testosterone (TT), bioavailable testosterone (BT), tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), IL-6 and IL-10 were measured and analysis made between men with 1, 2, or 3 vessel CAD, and between men with hypogonadal, borderline hypogonadal and eugonadal serum levels of testosterone.
In patients with 1, 2, or 3 vessel CAD, significant stepwise increases were observed in levels of IL-1beta: 0.16+/-0.03, 0.22+/-0.06, and 0.41+/-0.08 pg/ml (p=0.035), and IL-10: 0.93+/-0.11, 1.17+/-0.14, and 2.94+/-0.65 pg/ml (p=0.008). A significant stepwise increase in levels of IL-1beta was also observed in eugonadal, borderline hypogonadal, and hypogonadal men: 0.19+/-0.05, 0.29+/-0.05, and 0.46+/-0.13 pg/ml (p=0.047).
Consequently this data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that testosterone may regulate IL-1beta activity in men with CAD.
Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were -0.55/-0.57 mm Hg (Z-score -1.33, -2.00); for 2238 persons without medical or dietary intervention, -1.01/-0.98 mm Hg (Z -1.63, -2.25); for 2038 nonhypertensive persons from this sub-cohort, -0.91/-0.92 mm Hg (Z -1.80, -2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, -0.97/-0.87 mm Hg (Z -1.52, -1.95); blood pressure differences were -0.32/-0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels.
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