-
Carolina de Ciuceis,
Claudia Rossini,
Enzo Porteri,
Elisa la Boria,
Claudia Corbellini,
Francesco Mittempergher,
Ernesto di Betta,
Beatrice Petroboni,
Annamaria Sarkar,
Claudia Agabiti-Rosei,
Claudio Casella,
Riccardo Nascimbeni,
Rita Rezzani,
Luigi F Rodella,
Francesca Bonomini,
Enrico Agabiti-Rosei,
Damiano Rizzoni
[show abstract]
[hide abstract]
ABSTRACT: It is not known whether, in obesity, the capillary density or the number of circulating endothelial progenitor cells (EPCs) are reduced, or whether fibrosis of small vessels is also present. In addition, possible effects of weight reduction on these parameters have never been evaluated. Therefore, we investigated EPCs and capillary density in 25 patients with severe obesity, all submitted to bariatric surgery, and in 18 normotensive lean subjects and 12 hypertensive lean patients as controls. All patients underwent a biopsy of subcutaneous fat during bariatric surgery. In five patients, a second biopsy was obtained after consistent weight loss, about 1 year later, during a surgical intervention for abdominoplasty. EPCs and capillary density were reduced in obesity, and EPCs were significantly increased after weight reduction. Vascular collagen content was clearly increased in obese patients. No significant difference in vascular collagen was observed between normotensive obese patients and hypertensive obese patients. After pronounced weight reduction, collagen content was nearly normalized. No difference in stress-strain relation was observed among groups or before and after weight loss. In conclusion, our data suggest that microvascular rarefaction occurs in obesity. EPCs were significantly reduced in obese patients. Pronounced weight loss induced by bariatric surgery seems to induce a significant improvement of EPC number, but not of capillary rarefaction. A pronounced fibrosis of subcutaneous small resistance arteries is present in obese patients, regardless of the presence of increased blood pressure values. Consistent weight loss induced by bariatric surgery may induce an almost complete regression of microvascular fibrosis.
Blood pressure 01/2013; · 1.26 Impact Factor
-
Maria Lorenza Muiesan,
Massimo Salvetti,
Damiano Rizzoni,
Anna Paini,
Claudia Agabiti-Rosei,
Carlo Aggiusti,
Fabio Bertacchini,
Deborah Stassaldi,
Alice Gavazzi,
Enzo Porteri, Carolina De Ciuceis,
Enrico Agabiti-Rosei
[show abstract]
[hide abstract]
ABSTRACT: The possible relationships between indicators of small resistance artery structure and of arterial stiffness and central hemodynamics have not yet been evaluated. Aim of this study was to assess the relationship between indicators of large arteries stiffness, including carotido-femoral pulse wave velocity and of vascular alterations in small resistance arteries (media/lumen ratio, M/L) in patients with primary and secondary hypertension. In 73 patients (mean age, 53±14 years, 34 females, 25 with type 2 diabetes mellitus, 18 never treated) with essential (n=37) and secondary (n=36) hypertension, carotido-femoral pulse wave velocity was measured. In all patients, small resistance arteries were dissected from subcutaneous fat biopsies and mounted on an isometric myograph, for the measurement of the M/L. Pulse wave analysis was performed in 67 patients. M/L ratio was significantly related to brachial systolic blood pressure and pulse pressure (r=0.36 and 0.31, P<0.001, respectively) and to central systolic and pulse pressure (r=0.44 and 0.42, P<0.001, respectively). A positive correlation was observed between M/L ratio and carotido-femoral pulse wave velocity (r=0.45; P<0.001); this correlation remained statistically significant after adjustment for age and mean blood pressure. M/L ratio was also associated to aortic augmentation index (r=0.33; P=0.008), and this correlations remained statistically significant after adjustment for potential confounders. In hypertensive patients, the presence of structural alterations of small resistance arteries may be associated with the increase in large arteries stiffness and possibly contribute to an increase in central pressure by increasing the magnitude of wave reflections.
Hypertension 11/2012; · 6.21 Impact Factor
-
Damiano Rizzoni,
Enzo Porteri,
Sarah Duse, Carolina De Ciuceis,
Claudia Agabiti Rosei,
Elisa La Boria,
Francesco Semeraro,
Ciro Costagliola,
Adolfo Sebastiani,
Paola Danzi,
Guido A M Tiberio,
Stefano M Giulini,
Franco Docchio,
Giovanna Sansoni,
Annamaria Sarkar,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach.
We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r(2) = 0.57).
A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries.
Journal of hypertension 04/2012; 30(6):1169-75. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media to lumen ratio, are frequently present in hypertensive and/or diabetic patients. However, the evaluation of microvascular structure is not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. Media to lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the invasiveness of the assessment, since a biopsy of subcutaneous fat is needed. Non-invasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators has focused on the retinal microvascular bed. In particular, a non-invasive measurement of wall thickness to internal lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been recently introduced. Preliminary data suggest a fairly good agreement between this approach and micromyographic measurements, generally considered the gold standard approach. Therefore, the evaluation of microvascular structure is progressively moving from bench to bedside, and it could represent, in the immediate future, an evaluation to be performed in all hypertensive patients, in order to obtain a better stratification of cardiovascular risk.
High Blood Pressure & Cardiovascular Prevention 12/2011; 18(4):169-77.
-
[show abstract]
[hide abstract]
ABSTRACT: In cardiovascular and metabolic diseases, small resistance arteries may show the presence of structural alterations. In particular, in essential hypertension, an increased media-to-lumen ratio of subcutaneous small arteries with no change in the total amount of vascular wall tissue (eutrophic remodelling) has already been described several years ago. Similar alterations have been demonstrated also in patients with diabetes mellitus and obesity; in this case, however, a more evident contribution of vascular smooth muscle cell growth (hypertrophic remodelling) is present. This review addresses the effects of obesity on small resistance artery structure. Similar to diabetic patients, obese patients show an increased media-to-lumen ratio of subcutaneous small arteries, which appears associated with hypertrophic remodelling, as demonstrated by an increase in media cross-sectional area. Endothelial dysfunction evaluated as vasodilator response to acetylcholine has also been observed. Several studies have shown that increased media-to-lumen ratio of subcutaneous small resistance arteries possesses a prognostic significance in relation to cardiovascular outcome. Appropriate antihypertensive treatment may improve microvascular alterations both in essential hypertension and in type 2 diabetes mellitus. In obesity, a pronounced weight loss may improve microvascular structure. However, further studies are needed to elucidate the effects of other pharmacological and non-pharmacological interventions in obesity.
Basic & Clinical Pharmacology & Toxicology 08/2011; 110(1):56-62. · 2.18 Impact Factor
-
Carolina De Ciuceis,
Enzo Porteri,
Damiano Rizzoni,
Claudia Corbellini,
Elisa La Boria,
Gianluca E M Boari,
Annamaria Pilu,
Francesco Mittempergher,
Ernesto Di Betta,
Claudio Casella,
Riccardo Nascimbeni,
Claudia Agabiti Rosei,
Giuseppina Ruggeri,
Luigi Caimi,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media:lumen ratio, are frequently present in hypertensive and/or diabetic patients and may represent the earliest alteration observed. In addition, media:lumen ratios of small arteries have a strong prognostic significance. However, no data are available about the structure of small resistance arteries of obese patients, particularly after weight loss. We have investigated 27 patients with severe obesity. Twelve of them were normotensive, and 15 were hypertensive. All of the obese patients underwent bariatric surgery. We compared results obtained with those observed in 13 normotensive lean controls and in 13 hypertensive lean patients. All of the subjects and patients underwent a biopsy of subcutaneous fat during surgical intervention. In 8 obese patients, a second biopsy was obtained after consistent weight loss, during a surgical intervention for abdominoplasty. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and structural parameters were measured. A concentration-response curve to acetylcholine was performed to evaluate endothelial function. Obese patients, independent from the presence of hypertension, show the presence of an increased media:lumen ratio and media cross-sectional area, together with an impaired endothelial-dependent vasodilatation. After surgical correction of obesity and consistent weight loss, a significant improvement of microvascular structure and of some oxidative stress/inflammation markers were observed. In conclusion, our data suggest that the presence of obesity is associated with structural alterations of subcutaneous small resistance arteries, mainly characterized by hypertrophic remodeling. Weight loss may improve microvascular structure.
Hypertension 07/2011; 58(1):29-36. · 6.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND. In hypertensive patients, endothelial dysfunction is associated with an increased incidence of cardiovascular events. Calcium-channel antagonists can reverse impaired endothelium-dependent vasodilation in different vascular districts, while conflicting results are found in the brachial artery. Aim. To investigate the effect of barnidipine in comparison with hydrochlorothiazide on endothelial function of hypertensives, as assessed by flow-mediated vasodilation (FMD) of the brachial artery. METHODS. Patients with mild to moderate hypertension (age range 26-67 years) were randomized to receive barnidipine or hydrochlorothiazide. A thorough clinical examination, including blood pressure (BP) measurement, was performed at randomization as well as after 6, 12 and 24 weeks. FMD and 24-h BP monitoring was performed at randomization, after 12 and 24 weeks. RESULTS. After 12 and 24 weeks of treatment, a significant reduction in clinic BP was observed in both groups. Furthermore, a significant reduction in 24-h SBP and DBP was observed in patients receiving barnidipine but not in those receiving diuretic. The percentage change in FMD was different between the two groups of patients treated with barnidipine (at 12 weeks +1.2 ± 2.2%, p = 0.023 and at 24 weeks +1.25 ± 3.15%, p = 0.16 from baseline) or with hydrochlorothiazide (at 12 weeks -1.0 ± 3.0. p = 0.09 and at 24 weeks -1.78 ± 2.9%, p = 0.015 from baseline). A significant difference in FMD changes between the two groups was confirmed by analysis of covariance (p = 0.031). CONCLUSIONS. In presence of a similar clinic BP reduction, an improvement of endothelial function was observed during treatment with barnidipine but not with hydrochlorothiazide, suggesting that the barnidipine may exert a favourable effect on endothelial dysfunction in hypertensive patients.
Blood pressure 02/2011; 20(4):244-51. · 1.26 Impact Factor
-
Carolina de Ciuceis,
Annamaria Pilu,
Damiano Rizzoni,
Enzo Porteri,
Maria Lorenza Muiesan,
Massimo Salvetti,
Anna Paini,
Eugenia Belotti,
Francesca Zani,
Gianluca E M Boari,
Claudia Agabiti Rosei,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.
Blood pressure 11/2010; 20(2):77-83. · 1.26 Impact Factor
-
Gianluca E M Boari,
Damiano Rizzoni, Carolina De Ciuceis,
Enzo Porteri,
Daniele Avanzi,
Caterina Platto,
Monica Mazza,
Alida Brignani,
Claudia Agabiti Rosei,
Doris Ricotta,
Luigi Caimi,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: We have previously demonstrated that structural alterations in subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen ratio (M/L), are a potent predictor of cardiovascular events, and that a close correlation exists between serum creatinine and M/L. The aim of the present study was to assess whether M/L of subcutaneous small resistance arteries may predict subsequent changes in renal function in hypertensive patients.
Sixty participants (13 normotensive participants and 47 hypertensive patients) underwent a biopsy of subcutaneous fat. Resistance-sized arteries were dissected and mounted on a wire myograph, and M/L was measured. Patients were re-evaluated after a mean follow-up period of 8.6 years. Serum creatinine, blood urea nitrogen, and uric acid were measured; glomerular filtration rate (eGFR) was estimated according to Modification of Diet in Renal Disease formula.
At baseline, we observed significant correlations between M/L and serum creatinine, eGFR, blood urea nitrogen, systolic, diastolic, mean, and pulse pressure. In addition, we observed significant correlations between M/L and serum creatinine at follow-up (r = 0.57; P < 0.001), percentage changes in serum creatinine (r = 0.46; P < 0.001), eGFR at follow-up (r = -0.43; P < 0.001); percentage changes in eGFR, yearly changes in eGFR, blood urea nitrogen at follow-up, and uric acid at follow-up. A multivariate analysis in which all common cardiovascular risk factors were included showed that M/L ratio is the most potent predictor of changes in renal function.
Our data suggest that structural alterations in subcutaneous small arteries may predict the time course of changes in renal function during a follow-up period of about 9 years.
Journal of hypertension 09/2010; 28(9):1951-8. · 4.02 Impact Factor
-
Rita Rezzani,
Enzo Porteri, Carolina De Ciuceis,
Francesca Bonomini,
Luigi F Rodella,
Silvia Paiardi,
Gianluca E M Boari,
Caterina Platto,
Annamaria Pilu,
Daniele Avanzi,
Damiano Rizzoni,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentration-response curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects.
Hypertension 06/2010; 55(6):1373-80. · 6.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been suggested that in animal models, red wine may have a protective effect on the vascular endothelium. However, it is not known whether this effect is also present in human small vessels and whether it is specific for certain wines. The objective of this study is to compare the vasodilator effects in subcutaneous small resistance arteries of wines with different flavonoid content as well as of ethanol vs. wines in normotensive (NT) subjects and in patients with essential hypertension (EH).
Twenty-six EH and 27 NT were included in the study. Subcutaneous small resistance arteries were dissected and mounted on a micromyograph. Then we evaluated vasodilator responses as concentration-response curves (20, 30, and 50 microl) to the following items: (i) a red wine produced in small oak barrels ("en barrique": EB) (Barolo Oberto 1994), (ii) a red wine produced in large wood barrels (LB) (Barolo Scarzello 1989), (iii) a red wine produced in steel tanks (Albarello Rosso del Salento 1997), and (iv) a white wine produced in steel tanks in the presence or absence of an inhibitor of the nitric oxide (NO) synthase (L-NMMA 100 micromol/l).
A dose-dependent vasodilator effect of red wines (particularly EB and LB) was detected in both NT and HT. The observed response was not reduced after preincubation with L-NMMA.
Our results suggest red wines are more potent vasodilator than ethanol alone, possibly depending on the content of polyphenols or tannic acid. HT show similar responses compared with NT, indicating that red wine is not harmful in this population.
American Journal of Hypertension 04/2010; 23(4):373-8. · 3.18 Impact Factor
-
Evasio Pasini,
Vincenzo Flati,
Silvia Paiardi,
Damiano Rizzoni,
Enzo Porteri,
Roberto Aquilani,
Deodato Assanelli,
Giovanni Corsetti,
Silvia Speca,
Rita Rezzani, Carolina De Ciuceis,
Enrico Agabiti-Rosei
[show abstract]
[hide abstract]
ABSTRACT: Patients with metabolic syndrome (MetS) have an increased risk of cardiovascular disease. Data obtained from muscle biopsies have demonstrated altered insulin signaling (IS) in patients with MetS. The IS regulates critical cell functions including molecular-regulated cellular metabolite fluxes, protein and energetic metabolism, cell proliferation and apoptosis with consequent regulation of cell life including endothelial homeostasis and blood coagulation. However, little is known about blood cell IS in MetS patients. The aim of this study was to develop a method to evaluate IS in peripheral lymphocytes to identify altered intracellular molecules in patients with MetS to use as risk biomarkers of vascular thrombosis.
We investigated 40 patients with MetS and 20 controls. MetS was defined according to guidelines from the US National Cholesterol Education Program Adult Treatment Panel III. Blood samples were taken from all participants. Total mononuclear cells were isolated from peripheral blood using density gradient centrifugation. IS molecules were evaluated using Western blot analysis followed by computer-assisted densitometer evaluation.
Lymphocytes of MetS patients showed a reduced mTOR expression (the mammalian target of rapamycin) which is a fundamental molecule of IS. Major impairment of IS was confirmed by reduced upstream and downstream mTOR molecules which regulate fundamental cells metabolic functions.
In patients with MetS, we found a reduction of mTOR and other mTOR-related molecules involved in insulin resistance, cell repair, coagulation and vasculogenesis. A reduced expression of mTOR may reflect an increased risk of vascular thrombosis.
Cardiovascular Diabetology 01/2010; 9:46. · 3.35 Impact Factor
-
Damiano Rizzoni,
Enzo Porteri, Carolina De Ciuceis,
Luigi F Rodella,
Silvia Paiardi,
Nicola Rizzardi,
Caterina Platto,
Gianluca E M Boari,
Annamaria Pilu,
Guido A M Tiberio,
Stefano M Giulini,
Gaia Favero,
Rita Rezzani,
Claudia Agabiti Rosei,
Giuseppe Bulgari,
Daniele Avanzi,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome.
We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress.
Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels.
Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.
The Journal of clinical endocrinology and metabolism 10/2009; 94(12):5010-8. · 6.50 Impact Factor
-
Enzo Porteri,
Luigi F Rodella,
Rita Rezzani,
Damiano Rizzoni,
Silvia Paiardi, Carolina de Ciuceis,
Gianluca E M Boari,
Eleonora Foglio,
Gaia Favero,
Nicola Rizzardi,
Caterina Platto,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mg/Kg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mg/Kg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after preincubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p < 0.001) and this improvement was abolished by L-NMMA (ANOVA p < 0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability.
Clinical and Experimental Hypertension 10/2009; 31(7):560-71. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Macrovasculature and microvasculature are deeply interrelated, since microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure. In fact, preliminary data suggest that some index of large artery stiffness is related with the media to lumen ratio of subcutaneous small resistance arteries of hypertensive patients. Microvascular structural alterations and changes in the mechanical properties of the macrovessels represent potent predictors of prognosis. Hypertension-related damage to the micro- and macrovascular system may be corrected by pharmacological agents. Among them, beta-blocking agents and diuretics have a negligible effect on microvascular structure, while renin-angiotensin system antagonists and calcium entry blockers have favorable actions, improving large artery mechanics and possibly reducing central wave reflections.
Blood pressure 10/2009; 18(5):242-6. · 1.26 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Milan hypertensive rat strain (MHS) is a genetic strain in which cardiovascular phenotypes seem to be dependent, at least in part, on adducin gene polymorphisms. The aim of our study was to evaluate the structure, contractile responses and endothelium-dependent vasodilation in mesenteric small resistance arteries in 12-week-old MHS, (n=7), age-matched Milan normotensive rats (MNS, n=7) and congenic strains in which the DNA segments carrying the alpha-adducin locus from the MHS have been introgressed into the MNS (MNA, n=7). Systolic blood pressure (tail cuff) and left ventricular weight to body weight were measured. Mesenteric small arteries were dissected and mounted on a micromyograph; the media:lumen ratio was then calculated. Concentration-response curves to acetylcholine and to norepinephrine (NE) were created. Systolic blood pressure was significantly increased in the MHS and MNA strains compared with the MNS. No significant difference in mesenteric small resistance artery structure was observed among the groups; however, a slightly more elevated media:lumen ratio was observed in MNA compared with the MNS. In contrast, left ventricular weight to body weight was significantly increased and ACH-induced dilatation was significantly impaired in the MHS and in MNA compared with MNS. The concentration-response curve to NE in the MHS showed significantly reduced sensitivity to NE; however, maximum contraction was increased in the MHS vs. the other groups. The MHS presents cardiac (but not vascular) remodeling, endothelial dysfunction and a peculiar contractile response to NE, compared with the other groups. The systolic blood pressure increase and trend to vascular remodeling in MNA support the pathogenic role of alpha-adducin.
Hypertension Research 06/2009; 32(7):581-5. · 2.58 Impact Factor
-
Damiano Rizzoni, Carolina De Ciuceis,
Enzo Porteri,
Silvia Paiardi,
Gianluca E M Boari,
Pietro Mortini,
Claudio Cornali,
Marco Cenzato,
Luigi F Rodella,
Elisa Borsani,
Nicola Rizzardi,
Caterina Platto,
Rita Rezzani,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased media-to-lumen ratio of subcutaneous small resistance arteries has been demonstrated to predict the development of cardiocerebrovascular events in hypertensive patients. Alterations in the structure of small cerebral arteries have been demonstrated in animal models of experimental or genetic hypertension. However, no evaluation with reliable techniques has ever been performed in humans.
Twenty-eight participants were included in the present study: they were 13 hypertensive patients and 15 normotensive individuals. All participants underwent a neurosurgical intervention for benign or malign tumors. A small portion of morphologically normal cerebral tissue was excised from surgical samples and examined. Cerebral small resistance arteries (relaxed diameter around 200 mum) were dissected and mounted on an isometric and isobaric myograph, and the tunica media to internal lumen ratio was measured. In addition, cerebral cortical microvessel density (MVD) was also evaluated. The tissue was sectioned and stained for CD31, and MVD was measured with an automated image analyzer (percentage of area stained). Blood pressure values were evaluated, before surgical intervention, by standard sphygmomanometry.
M/L was significantly greater and MVD significantly lower in hypertensive patients than that in normotensive individuals. No difference between groups in collagen content or mechanical properties of cerebral small arteries was observed.
Our results indicate that structural alterations of small cerebral vessels are present in hypertensive patients compared with normotensive individuals, similar to those previously observed in subcutaneous small arteries.
Journal of hypertension 05/2009; 27(4):838-45. · 4.02 Impact Factor
-
Silvia Paiardi,
Luigi F Rodella, Carolina De Ciuceis,
Enzo Porteri,
Gianluca E M Boari,
Rita Rezzani,
Nicola Rizzardi,
Caterina Platto,
Guido A M Tiberio,
Stefano M Giulini,
Damiano Rizzoni,
Enrico Agabiti-Rosei
[show abstract]
[hide abstract]
ABSTRACT: No data are presently available about changes in capillary density in the skeletal muscle and in the brain of spontaneously hypertensive rats (SHR) in relation to the development of hypertension.
We have investigated 4 week-old and 12 week-old SHR and age-matched normotensive Wistar-Kyoto controls (WKY). Microvessel density (MVD) in the cerebral cortex and in a skeletal muscle were evaluated in sections stained for CD31. We also evaluated MVD in the dermal tissue of normotensive subjects and essential hypertensive patients. Subcutaneous small resistance arteries were dissected and mounted in a micromyograph and the media to lumen ratio (M/L) was measured.
A significant reduction in MVD in the skeletal muscle and in the brain of SHR was clearly observed at 12 weeks of age, after the development of hypertension, but not at 4 weeks of age (pre-hypertensive condition). In hypertensive patients a significant reduction in the dermal MVD and an inverse correlation between M/L and MVD was observed.
Our results suggest that, in the brain and skeletal muscle of adult SHR after the development of hypertension, and in the derma of adult essential hypertensive patients microvascular rarefaction may occur.
Clinical hemorheology and microcirculation 02/2009; 42(4):259-68. · 3.40 Impact Factor
-
Gianluca E M Boari,
Nicola Rizzardi, Carolina de Ciuceis,
Caterina Platto,
Silvia Paiardi,
Enzo Porteri,
Anna Paini,
Massimo Salvetti,
Maria Lorenza Muiesan,
Damiano Rizzoni,
Enrico Agabiti Rosei
[show abstract]
[hide abstract]
ABSTRACT: It has been previously demonstrated that structural alterations of subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen (M/L) ratio, is the most potent predictor of cardiovascular events. The aim of the present study was to identify possible determinants of small resistance artery structure that may be evaluated with non-invasive approaches.
One hundred and ninety-nine subjects (normotensives, essential hypertensives and patients with secondary hypertension) were included in the present study. All subjects were submitted to a biopsy of subcutaneous fat from the gluteal or the anterior abdominal region. Small resistance arteries were dissected and mounted on an isometric myograph, and M/L ratio was measured. All patients underwent standard biochemical tests, clinic blood pressure measurement, standard echocardiography and 24-h ambulatory blood pressure measurement. Glomerular filtration rate (GFR) was calculated according to MDRD study formula and Cockroft's formula.
Significant correlation was found between M/L ratio and, respectively: GFR calculated both with MDRD study formula and Cockroft-Gault formula, creatinine serum, blood urea nitrogen, glycaemia, circulating sodium, clinical pulse pressure, stroke volume to pulse pressure ratio, clinical systolic, diastolic and mean arterial pressure, daytime pulse pressure. However, in a multivariate regression analysis, only serum creatinine remained in the model, and proved to be an independent predictor of small artery structure.
Indices of renal function and, probably, of large artery distensibility may be related to small arteries remodelling in hypertension.
Blood pressure 10/2008; 17(4):204-11. · 1.26 Impact Factor
-
Damiano Rizzoni,
Evasio Pasini,
Vincenzo Flati,
Luigi F Rodella,
Silvia Paiardi,
Deodato Assanelli, Carolina De Ciuceis,
Enzo Porteri,
Gianluca Em Boari,
Rita Rezzani,
Silvia Speca,
Gaia Favero,
Stefano Martinotti,
Elena Toniato,
Caterina Platto,
Enrico Agabiti-Rosei
[show abstract]
[hide abstract]
ABSTRACT: Spontaneously hypertensive rats are an example of an animal model of genetic hypertension with insulin resistance. The aim of this study was to investigate insulin signaling in the heart and in the skeletal muscle of spontaneously hypertensive rats, as well as to evaluate the effects of renin-angiotensin system blockade.
We investigated eight untreated spontaneously hypertensive rats of 12 weeks of age and eight age-matched normotensive Wistar-Kyoto controls. In addition, eight spontaneously hypertensive rats were treated for 8 weeks with the angiotensin receptor blocker olmesartan, and eight spontaneously hypertensive rats with the angiotensin-converting enzyme inhibitor enalapril. The heart and a skeletal muscle (quadriceps femoris) were promptly dissected and frozen. Insulin signaling was evaluated by Western blot analysis of involved proteins; in addition, microvessel density was indirectly evaluated by immunohistochemistry.
Blood pressure values were normalized by both olmesartan and enalapril. In the heart, no statistically significant difference in the expression of proteins involved in insulin signaling was observed between untreated spontaneously hypertensive rats and Wistar-Kyoto controls. On the contrary, in the skeletal muscle of untreated spontaneously hypertensive rats, we noted a significant reduction of insulin receptors, of insulin-receptor substrate-1, and of phosphorylated-mammalian target of rapamycin. The treatment with olmesartan normalized insulin signaling, including expression of glucose transporter-4, whereas the treatment with enalapril was ineffective for the insulin receptor and less effective than olmesartan on the insulin-receptor substrate-1, phosphorylated-mammalian target of rapamycin and glucose transporter-4. There was a significant reduction in microvessel density in the skeletal muscle of spontaneously hypertensive rats compared with Wistar-Kyoto controls, and this was completely prevented by both olmesartan and enalapril.
These results suggest that changes in insulin signaling occur in the skeletal muscle but not in the heart of untreated spontaneously hypertensive rats. In the skeletal muscle, insulin signaling was restored by olmesartan, whereas enalapril was less effective. Effective antihypertensive treatment with olmesartan or enalapril was associated with prevention of microvascular rarefaction.
Journal of Hypertension 09/2008; 26(8):1595-601. · 4.02 Impact Factor
