DETERMINANTS OF INTERINDIVIDUAL VARIATION OF RENIN AND PRORENIN CONCENTRATIONS - EVIDENCE FOR A SEXUAL DIMORPHISM OF (PRO)RENIN LEVELS IN HUMANS

Background Plasma renin concentrations are an important factor in card iovascular risk profiling, Objective To investigate the effects of sex , medication, and anthropometric factors that may contribute to the in terindividual variation in the plasma concentrations of renin and its precursor prorenin, Design and methods Prorenin and renin levels in 32 7 men and 383 women, aged 52-69 years, who participated in a 1994 reex amination of a previous population survey in Bavaria, were measured by immunoradiometric assay. Results Prorenin and renin levels in men wer e significantly higher than those in women, those in women without est rogen replacement therapy were significantly higher than those in wome n with estrogen replacement therapy, and those in diabetics were signi ficantly higher than those in nondiabetics. Prorenin level was correla ted negatively to blood pressure and positively to age and the use of diuretics; it was normal in subjects using angiotensin converting enzy me inhibitors and beta-adrenergic antagonists (beta-blockers), Renin l evel was correlated negatively to atrial natriuretic peptide level and the use of beta-blockers, and it was elevated above normal revels in subjects using angiotensin converting enzyme inhibitors and diuretics as well as in subjects who had previously suffered myocardial infarcti on, After exclusion of data for women being administered estrogen repl acement therapy, multivariate analysis revealed that sex (P< 0.001), a ge (P< 0.02), blood pressure (P< 0.002), diabetes (P < 0.05), and the use of angiotensin converting enzyme inhibitors (P < 0.002), beta-bloc kers (P < 0.001), and diuretics (P < 0.05) were independent determinan ts of plasma prorenin, Plasma renin was independently related to atria l natriuretic peptide level (P< 0.01) and the use of angiotensin conve rting enzyme inhibitors (P < 0.001), beta-blockers (P < 0.001), and di uretics (P < 0.05), Conclusions These data demonstrate that there is a sexual dimorphism of prorenin levels in humans, suggesting that sex h ormones affect the regulation of the renin gene, Data confirm previous reports of elevated prorenin levels in diabetics and older subjects, as well as of lower than normal prorenin levels in subjects with hyper tension in smaller populations, Our findings may help to clarify the p otential (patho)physiologic functions of prorenin and to identify the factors that influence the constitutive secretion and intracellular pr ocessing of this prohormone, (C) 1998 Lippincott-Raven Publishers.