R García-Robles

Hospital Universitario Ramón y Cajal, Madrid, Madrid, Spain

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Publications (68)179.09 Total impact

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    ABSTRACT: Goal blood pressure (BP) was defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) and the World Health Organization-International Society of Hypertension (WHO/ISH) as <140 mm Hg systolic and <90 mm Hg diastolic for the general and <130 mm Hg systolic and <85 mm Hg diastolic for special high-risk populations. However, there are few reports that address BP control among special subgroups of hypertensives by reference to targeted BP. We therefore conducted a study to evaluate BP control of 4049 hypertensives in 47 hospital-based hypertension units in Spain. Overall, 42% of patients achieved goal BP (<140 mm Hg systolic and <90 mm Hg diastolic). Only 13% of diabetic patients and 17% of those with renal disease achieved the BP goal (<130 mm Hg systolic and <85 mm Hg diastolic), and only 10% and 12%, respectively, achieved the even more rigorous goal (<130 mm Hg systolic and <80 mm Hg diastolic). Likewise, only 18% of patients in JNC-VI risk group C and 17% of WHO/ISH high-risk patients attained a goal BP <130 mm Hg systolic and <85 mm Hg diastolic. BP control (<125 mm Hg systolic and <75 mm Hg diastolic) was extremely low (2%) in patients with proteinuria >1 g/d. Poorer BP control was observed among patients at high risk, with diabetes, renal disease, or obesity, than in lower-risk groups. BP control was lower for systolic than for diastolic BP. In >50% of uncontrolled patients, no measures were taken by doctors to optimize pharmacologic treatment, and approximately one-third of patients were still using drug monotherapy. Control of BP, particularly of systolic BP, is still far from optimal in hospital-based hypertension units. Patients at high risk, with diabetes or proteinuria, warrant focused attention. Moreover, a more aggressive behavior of doctors treating uncontrolled hypertension is needed.
    Hypertension 07/2004; 43(6):1338-44. · 6.87 Impact Factor
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    ABSTRACT: To evaluate cardiovascular functionality in patients with thyroid cancer, we have performed echocardiography and ambulatory blood pressure monitoring in 19 women with differentiated thyroid carcinoma during thyroxine withdrawal, at three time points: the last day on TSH-suppressive thyroxine doses (subclinical or mild hyperthyroidism), 4-7 days after withdrawal (normal free thyroxine (FT4) and free triiodothyronine (FT3) levels), and before 131I whole body scanning (overt hypothyroidism). Twenty-one healthy euthyroid women served as controls. When compared with the values at visit 2, when patients had normal serum FT4 and FT3 levels, night-time systolic and mean blood pressure were increased when the patients were mildly hyperthyroid, and night-time systolic, diastolic and mean blood pressure were increased during overt hypothyroidism. The proportion of nondippers (absence of nocturnal decline in blood pressure) was markedly increased compared with healthy controls (7%), when patients were hyper- or hypothyroid (58% and 50% respectively), but not when patients had normal FT4 and FT3 levels (12%). No changes were observed in office blood pressure or in daytime ambulatory blood pressure readings. Diastolic function worsened during thyroxine withdrawal (E and A waves (early and late mitral flow) decreased, and the E/A ratio and the isovolumic relaxation time increased), and cardiac output decreased in parallel with the decrease in heart rate and systolic blood flow. In conclusion, the chronic administration of TSH-suppressive doses of thyroxine and the withdrawal of thyroxine frequently used for the management of differentiated thyroid carcinoma, are associated with undesirable cardiovascular effects.
    Endocrine Related Cancer 07/2004; 11(2):345-56. · 5.26 Impact Factor
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    ABSTRACT: P-377Key Words: Diabetic Retinopathy, AT-1 Receptors, Irbesartan
    01/2004;
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    ABSTRACT: Recent evidence highlights the relationship between metabolic syndrome (MS) and increased risk of cardiovascular (CV) diseases. Mild renal function abnormalities are associated with an enhanced CV risk, considered to be due to the presence of associated risk factors. Hence, MS and renal abnormalities could be linked and contribute to augment CV risk. For estimating the prevalence of diminished creatinine clearance (CC; <60 ml/min per 1.73 m(2)) in hypertensive patients with or without MS and for investigating the factors accompanying this abnormality, 1625 hypertensive patients, aged 18 yr or older, were included. The presence of MS was defined according to the Adult Treatment Panel III criteria. The overall prevalence of MS was 49.4% (n = 802). No significant difference was found for CC between those with and without MS, albeit the presence of MS was accompanied by greater urinary albumin excretion (P = 0.01). The prevalence of a diminished CC was also similar in the two groups. MS-positive patients presented a progressive decay in CC when classified as normoglycemic (n = 319), impaired fasting glucose (n = 237), and diabetic patients (n = 246; 85.9 +/- 30.2, 81.8 +/- 26.8, and 75.2 +/- 25.7 ml/min per 1.73 m(2), respectively; P = 0.0007 linearity test) and the opposite for microalbuminuria (29.5 +/- 45.5, 45.0 +/- 96.6, and 74.1 +/- 146.3 mg/24 h, respectively; P = 0.001 linearity test). In multiple regression analysis, factors related to the finding of a diminished CC in MS and non-MS patients were similar. Hypertensive patients at a relatively young age present with an elevated prevalence of minor abnormalities of renal function that is mostly related to the presence of metabolic alteration of glucose together with age and BP.
    Journal of the American Society of Nephrology 01/2004; 15 Suppl 1:S37-42. · 8.99 Impact Factor
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    ABSTRACT: Hypertension is the main risk factor for the progression of kidney damage in diabetes mellitus. The aim of the present work is to compare the effect of the treatment with irbesartan (IRBE) and omapatrilat (OMA), in obese Zucker rats (OZR). A group of 45 OZR were uninephrectomized to accelerate renal damage, and divided into three groups: two experimental groups (IRBE and OMA) treated with 50 and 40 mg/kg/d, respectively; and the control group (CG). At the end of the 8-month follow-up period, animals were killed and the remnant kidney was removed for histologic study and to evaluate the transforming growth factor-beta1 (TGF-beta1) expression. Both therapies reduced blood pressure (BP) versus CG (P <.001). Moreover, systolic BP was significantly lower in the OMA group than in the IRBE group (P <.001). Also, both treatments significantly lowered the urinary albumin excretion (P <.001). The OMA treatment exhibited lower values than the IRBE treatment (P <.05). The kidney TGF-beta1 expression was reduced by both treatments to a similar level. The correlation between systolic BP and glomerulosclerosis (GS) is very high (r = 0.90; P <.0001). Also, a high correlation was observed between GS and proteinuria (r = 0.79, P <.0001). The correlation between systolic BP and proteinuria was weaker (r = 0.69; P <.01). These data suggest that both therapies are effective in ameliorating the progression of renal damage in this experimental model. Omapatrilat affords greater long-term renoprotection than irbesartan, mainly due to its potent effect in reducing systolic BP.
    American Journal of Hypertension 11/2003; 16(11 Pt 1):979-85. · 3.67 Impact Factor
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    ABSTRACT: Hyperuricemia can be the consequence of an increased urate production, a decreased renal excretion, or both. An increased prevalence of hyperuricemia has been described in essential hypertensive patients partly due to a decreased renal urinary urate excretion (UUE). Hyperuricemia has been shown to be associated with an increased risk of cardiovascular disease in hypertensive patients in some but not in all epidemiological studies in which this relationship has been investigated. To assess the influence of low UUE in the association between serum urate, renal function and hypertension severity. This cross-sectional study was carried out in a sample of 677 male hypertensive patients, aged 35-60 years, with essential arterial hypertension consecutively attended in a hospital hypertension unit. The presence of hypertension-related organ damage at diagnosis was classified according to classical WHO criteria as grade 1, 2 or 3. Urate underexcretion was defined as 24-h urinary urate below the product serum urate x 100. Mean serum urate levels were 6.4 +/- 1.6 mg/dl in the total sample. Hyperuricemia (serum urate >7 mg/dl) was present in 28.5% of patients and only 17.0% had underexcretory hyperuricemia. This subgroup of patients exhibited the higher rate of hypertension-related target organ damage (TOD). A multivariate analysis, showed that underexcretory hyperuricemia but not hyperuricemia remained an independent predictor of TOD (odds ratio 2.5. 95% CI 1.6-3.89). Serum urate correlated positively with serum creatinine in hyperuricemic patients (r = 0.50, p < 0.001), but not in patients with underexcretory hyperuricemia (r = 0.21, p = 0.18). Underexcretory hyperuricemia is strongly related to hypertensive organ damage and this relationship does not seem to be mediated by a decreased renal function. This aspect could underline the predictive value of hyperuricemia independently of serum creatinine. UUE could improve the clinical predictive value of hyperuricemia as a cardiovascular risk factor.
    Blood Pressure 02/2003; 12(5-6):277-83. · 1.39 Impact Factor
  • Jose Sancho, Olga Gonzalez, Rafael Garcia-Robles
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    ABSTRACT: We have isolated, in parallel, from bovine hypothalamic and adrenal tissue endogenous Ouabain and the sodium pump inhibitor HHIF that is structurally different from ouabain. The purification protocol consisted in a lipophilic chromatography, followed by lipid extraction, semipreparative and analytical reverse phase high pressure liquid chromatography (HPLC).The bioassays used were “in vitro” Na+/K+-ATPase inhibition, and 3H-ouabain displacement from its specific binding site in the enzyme structure as well as inhibition of 86Rb uptake from human red blood cells. We have obtained from both tissues, a low molecular weight, nonpeptidic, nonlipidic substance that elutes as a single peak highly pure according to the purity criteria of coincidence of spectra in both slopes and the top. This substance that elutes at 67% AcN has a UV absorption spectra with 2 maximum of absorbance at 210 and 280 nm. This substance inhibits the sodium pump, displaces tritiated ouabain from its receptor on the enzyme and, in early purification steps, cross-reacts with digoxin antibodies losing this property when higher purification level are reached. It also inhibits Ca++/Mg++ ATPase of synaptosomes from rat brain and Ca++/Mg++ ATPase from sarcoplasmic reticulum. It is also present in bovine adrenal tissue and in human placenta.With the same purification procedure we have isolated from bovine central nervous and adrenal tissue ouabain that elutes prior to HHIF in the final purification HPLC systems. This endogenous ouabain has, in all the systems tested, the same chromatographic behaviour that cold or titriated synthetic ouabain. The concentration in adrenal tissue is 10 times higher that in brain. By mass spectrometric analysis this endogenous ouabain is indistinguishable from sinthetic ouabain.The behaviour of binding to different anti-ouabain or anti-digoxin antibodies was the same for ouabain isolated fron brain adrenal or synthetic ouabain. By mass spectrometric analysis HHIF revealed a single unique molecular ion with an accurate mass of 412.277 and a mass spectra different from ouabain.
    American Journal of Hypertension - AMER J HYPERTENS. 01/2003; 16(5).
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    ABSTRACT: The present study assessed the prevalence, awareness, treatment and control of hypertension among the elderly population of Spain. Based on a nationally representative sample of 4009 individuals aged 60 years, two sets of six blood pressure measurements were obtained by trained observers at each subject's home, using standardized methods. In each set, three mercury-based measurements were alternated with three automated measurements. The mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) was 143/79 mmHg, and the pulse pressure was 64 mmHg. The prevalence rate of hypertension (SBP 140 mmHg, DBP 90 mmHg, or current drug treatment) was 68.3%. No result obtained was sensitive to a particular measurement device. Of the hypertensives, 65% were aware of their condition, 55.3% were treated and 16.3% were controlled. Among treated hypertensives, SBP control (32.2%) was much lower than DBP control (82.3%). Control was lower in men than in women, in older than in younger subjects, and in those with lowest than in those with higher educational levels. About 57% of uncontrolled treated hypertensives were on monotherapy. Weight loss was among the least heeded items of advice (39% among overweight hypertensives). Hypertension is a major public health problem in elderly Spaniards. Most hypertensives had their hypertension uncontrolled. Greater emphasis should be laid on the most disadvantaged (the older, men, and those with lowest education) in terms of hypertension management, and on reinforcing weight loss and combining drugs for enhanced hypertension control.
    Journal of Hypertension 12/2002; 20(11):2157-64. · 3.81 Impact Factor
  • Luis M Ruilope, Rafael Garcia-Robles, Basilio Moreno
    Blood Pressure 02/2002; 11(5):260-2. · 1.39 Impact Factor
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    ABSTRACT: This study assessed the prevalence, awareness, treatment and control of hypertension among the elderly population of Spain. Based on a nationally representative sample of 4009 individuals aged over 60 years, two sets of six blood pressure measurements were obtained by trained observers at each subject's home, using standardized methods. In each set, 3 mercury-based measurements were alternated with 3 automated-based measurements. Prevalence rate of hypertension (SBP = or greater than 140 mm Hg, DBP = or greater than 90 mm Hg, or current drug treatment) was 68.3%, and that of isolated systolic hypertension 42.8%. No result obtained was sensitive to a particular measurement device. Of the hypertensives, 65% were aware of their condition, 55.3% were treated and 16.3% controlled. Among treated hypertensives, SBP control (32.2%) was much more lower than DBP control (82.3%). Control was lower in men than in women, in older than in younger subjects, and in those with lowest than in those with higher educational levels. About 57% of uncontrolled treated hypertensives were on monotherapy. Weight loss was among the least heeded items of advice (39% among overweight hypertensives). In conclusion, hypertension is a major public health problem in elderly Spaniards. Most hypertensives had their hypertension uncontrolled. Greater emphasis should be laid on the most disadvantaged (the older, men, and those with lowest education) in terms of hypertension management, and on reinforcing weight loss and combining drugs for enhanced hypertension control.
    American Journal of Hypertension - AMER J HYPERTENS. 01/2002; 15(4).
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    O González-Albarrán, R García-Robles
    Diabetes Care 12/2001; 24(11):1998-2000. · 7.74 Impact Factor
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    Diabetes Care 08/2001; 24(7):1297-9. · 7.74 Impact Factor
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    ABSTRACT: Hyperuricemia has been associated with an increased risk of cardiovascular disease in hypertensive patients. However, the relation between serum urate and severity of hypertension has not been conclusively defined as yet. We aimed at finding out whether there exists an independent relationship between changes in the prevalence of hyperuricemia and severity of hypertension. We studied 3 cohorts of patients aged 35 to 60 years with essential hypertension diagnosed at a university hospital in Madrid, Spain. The first cohort (before 1981) included 325 patients, the second (from 1981 to 1989) comprised 271 patients and the third cohort (from 1990 to 1999) included 545 patients. Disease severity ranged from 1 to 6 according to blood pressure levels at diagnosis (WHO/ISH grades 1, 2 or 3 were assigned 1, 2 or 3 points, respectively) and target organ damage (left ventricular hypertrophy, hypertensive retinal vascular changes, and proteinuria above 300 mg/day; one point each). Mean serum urate concentrations in the 3 cohorts were 6.6, 5.8 and 5.5 mg/dL, respectively (p < 0.05 for all comparisons). 39% of patients in the first cohort had a serum urate concentration > 7.0 mg/dL whereas only 18.1% patients in the third group showed hyperuricemia (difference: 20.9%; 95% CI, 10.1 to 32.3; p < 0.05). Severity of hypertension was higher in the first cohort (mean SD, 2.50 1.31 points) than in the third group (1.96 1.06 points; p < 0.05), with the second cohort showing an intermediate severity (2.23 1.01 points). Serum urate levels were directly related to the severity of hypertension in the 3 groups (r = 0.08, p < 0.05). In a multivariate analysis, after adjustment for confounding variables, serum urate had no significant association with severity of hypertension. However, target organ damage, systolic blood pressure and serum creatinine were all independent predictors of severity. Favourable changes in the severity of hypertension for a time period significantly correlate with decreases in hyperuricemia prevalence in the same period. On the other hand, hyperuricemia appears to be an indirect marker of hypertensive renal damage.
    Medicina Clínica 07/2001; 117(3):85-9. · 1.40 Impact Factor
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    ABSTRACT: The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disor- ders (16 had PCOS, and 17 had hirsutism without menstrual dys- function). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum andro- stenedione levels, but had normal serum sex hormone-binding glob- ulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 dia- betic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hy- perandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hir- sutism. (J Clin Endocrinol Metab 85: 4182- 4187, 2000)
    Obstetrical and Gynecological Survey 04/2001; 56(5):282-283. · 2.51 Impact Factor
  • G Piédrola, E Novo, F Escobar, R García-Robles
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    ABSTRACT: White blood cell (WBC) count has been shown as a risk factor for cardiovascular disease. Decreased insulin sensitivity has been suggested as the link between these two entities. Our aim was to study the potential relation between insulin sensitivity and WBC count in patients with coronary artery disease. In order to assess insulin sensitivity, we performed 83 insulin suppression tests before and after therapy in 50 patients with coronary artery disease. Patients with glucose intolerance, arterial hypertension or obesity were excluded. Steady-state plasma glucose (SSPG) and insulin sensitivity index (ISI=1 000 x glucose infusion rate/SSPG) were considered as a measure of insulin sensitivity. WBC count, blood platelets, fibrinogen, microalbuminuria, creatinine, urea and HbA1c were also assessed. Simple and multiple correlation analysis were carried out between insulin sensitivity parameters and the other variables measured. There were significant correlation between SSPG and WBC count (r=0,32: p=0,003) and microalbuminuria (r=0,28: p=0,012). We also found statistically significant correlation between ISI and WBC count (r=0,27: p=0,015) and microalbuminuria (r=0,24: p=0,029). No correlation could be detected between either SSPG or ISI and the other variables measured. In multiple regression analysis, WBC count was found to be an independent predictor of both SSPG (p<0.01) and ISI (p<0.05). Our data show the existence of a significant relationship between decreased insulin sensitivity and WBC count in patients with coronary artery disease. The results of this study suggest that an elevated WBC count could be postulated as part of the insulin resistant syndrome.
    Annales d Endocrinologie 03/2001; 62(1 Pt 1):7-10. · 1.02 Impact Factor
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    ABSTRACT: The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism.
    Journal of Clinical Endocrinology &amp Metabolism 12/2000; 85(11):4182-7. · 6.43 Impact Factor
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    ABSTRACT: The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) x 10(3). A second insulin suppression test was performed after 6 months' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients. There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.
    Postgraduate Medical Journal 02/1999; 75(879):27-31. · 1.61 Impact Factor
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    ABSTRACT: Human obesity, which is very common in Polycystic Ovaries Syndrome and in "X Syndrome", constitutes an insulin-resistance state in which multiple clinical, biochemical and hemodynamic alterations coexist. Insulin resistance in the obese has been recently associated with an endothelial dysfunction. To investigate the possibility that clinical and metabolic derangements related to insulin resistance could induce changes in vascular blood flows, we have studied the levels of mesenteric (MBF), renal (RBF) and femoral (FBF) blood flows in Beagle dogs kept for 2 years on a normal (control group) or high fat diet (obese group). This experimental model exhibits many of the abnormalities with the human syndrome. In addition, we have tested the effects of chronic treatment with captopril (capto group) in monotherapy or in association with pravastatin (prava+capto group) on the hemodynamic changes associated with this diet. After the two year follow-up, Transonic flow probes were placed around the three arteries to measure basal blood flows and their response to a hyperinsulinemic-normoglycemic test in anesthetized animals. During this test the degree of insulin sensitivity was estimated. In association with higher body weight, blood pressure, insulin resistance, and fasting levels of insulin and total cholesterol, the obese group exhibited decreased basal levels of FBF and a greater femoral vasoconstriction during hyperinsulinism (P < 0.05 vs control). Combined therapy with captopril and pravastatin ameliorated the reduction in basal FBF and hyperinsulinism-induced vasoconstriction (P < 0.05), in addition to the beneficial effects on insulin sensitivity, and clinical and metabolic parameters. Synergistic beneficial effects of both drugs on lipid and carbohydrate profiles may account for this positive outcome, by attenuating the atherogenic process associated with this model.
    The Journal of Steroid Biochemistry and Molecular Biology 01/1999; 69(1-6):273-9. · 3.98 Impact Factor
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    ABSTRACT: Angiotensin-converting enzyme inhibitors (ACEI) block degradation of bradykinin, and bradykinin stimulates prostacyclin synthesis. Therefore, we set out to determine whether the effects of ACE inhibitors on prostaglandin production in essential hypertensive patients are class effects or are dependent on ACE inhibitor structure. In addition, we studied whether hypertensives show an impaired capacity to synthesize vasodilator prostaglandins. To address these questions, we compared the effects of captopril (sulfhydryl-containing inhibitor), enalapril and ramipril (carboxyl-containing inhibitors) and fosinopril (phosphoryl-containing inhibitor) on blood pressure and urinary excretion of 6-keto-prostaglandin (PG) F1-alpha (the breakdown product of prostacyclin) in 44 mild-to-moderate essential hypertensive subjects before and 8 weeks after administration of an ACEI. We also studied prostacyclin excretion in 15 normotensive healthy controls. Levels of urinary 6-keto-PGF1-alpha (pg/ml) were measured by specific radioimmunoassay. Hypertensive subjects showed a lower excretion of 6-keto-PGF1-alpha than normotensive controls (212+/-147 vs 353+/-98 pg/ml, p < 0.001). All ACEI induced a significant decrease in MAP and increased the rate of excretion of the prostacyclin metabolite: C, 211+/-200 to 338+/-250 pg/ml, p < 0.05; E, 202+/-133 to 296+/-207 pg/ml, p < 0.05; R, 205+/-127 to 342+/-211 pg/ml, p < 0.05; F, 235+/-128 to 347+/-241 pg/ml, p < 0.05. In hypertensives (n = 44) the decrease in blood pressure correlated negatively with the rise in 6-keto-PGF1-alpha excretion (r = -0.51, p < 0.001). These data suggest that impaired prostacyclin biosynthesis in hypertensive patients could account for haemodynamic changes leading to the hypertensive state. Moreover, the hypotensive mechanisms of ACEI may be mediated by an increase in prostacyclin production; this effect seems to be class-dependent.
    Blood Pressure 01/1999; 8(5-6):279-84. · 1.39 Impact Factor
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    ABSTRACT: To study the insulin-like growth factor-1 (IGF-1) axis in hirsute women. Controlled clinical study. Tertiary care institutional hospital. Forty hirsute women and 17 women with normal menstrual cycles. Basal and ACTH-stimulated samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after a single 3.75-mg IM dose of triptorelin. Controls did not receive triptorelin for ethical reasons. Serum GH, IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, glucose, total testosterone, sex hormone-binding globulin, E2, and gonadotropin levels. Basal and ACTH-stimulated steroid precursors were measured. Patients with idiopathic hirsutism were identified by normal serum androgen levels (n=17). Those with functional ovarian hyperandrogenism (n=15) were identified by an increase in the serum testosterone level that normalized during gonadal suppression, whereas those with functional adrenal hyperandrogenism (n=8) were identified by an initial increase in the testosterone level that persisted during gonadal suppression. The adrenal hyperandrogenism group had increased IGF-1 levels compared with the control, idiopathic hirsutism, and ovarian hyperandrogenism groups. Patients with ovarian hyperandrogenism had normal TGF-1 concentrations, but their IGFBP-3 concentrations were lower than those of controls. No differences were observed in GH levels between any of the groups. These results persisted when the influence of age was corrected for. The IGF-1 axis appears to be involved in the pathogenesis of hyperandrogenism, especially in patients with adrenal hyperandrogenism, who have a clear increase in IGF-1 levels. Moreover, patients with ovarian hirsutism have decreased IGFBP-3 concentrations, which might enhance IGF-1 bioavailability.
    Fertility and Sterility 01/1999; 70(6):1090-100. · 4.17 Impact Factor

Publication Stats

731 Citations
179.09 Total Impact Points

Institutions

  • 1987–2003
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 1990–2001
    • Hospital 12 de Octubre
      • Servicio de Nefrología
      Madrid, Madrid, Spain
  • 1998
    • Cajal Institute
      Madrid, Madrid, Spain
    • Hospital General Universitario de Alicante
      • Departamento de Endocrinología
      Alicante, Valencia, Spain