High plasma prorenin in non diabetic siblings of non insulin-dependent diabetes mellitus patients.

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p<0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p<0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.

Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia.

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.

The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study.

The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the alpha-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the alpha-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp alpha-adducin allele. The alpha-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (P=0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (P<0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of alpha-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the alpha-adducin genotype with hypertension in Sassari.