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Determinants of interindividual variation of renin and prorenin concentrations: evidence for a sexual dimorphism of (pro)renin levels in humans

Jan Danser, A H.1,5; Derkx, Frans H.M.2; Schalekamp, Maarten A.D.H.2; Hense, Hans-Werner3; Riegger, Günter A.J.4; Schunkert, Heribert4

Original article
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Background Plasma renin concentrations are an important factor in cardiovascular risk profiling.

Objective To investigate the effects of sex, medication, and anthropometric factors that may contribute to the interindividual variation in the plasma concentrations of renin and its precursor prorenin.

Design and methods Prorenin and renin levels in 327 men and 383 women, aged 52–69 years, who participated in a 1994 reexamination of a previous population survey in Bavaria, were measured by immunoradiometric assay.

Results Prorenin and renin levels in men were significantly higher than those in women, those in women without estrogen replacement therapy were significantly higher than those in women with estrogen replacement therapy, and those in diabetics were significantly higher than those in nondiabetics. Prorenin level was correlated negatively to blood pressure and positively to age and the use of diuretics; it was normal in subjects using angiotensin converting enzyme inhibitors and β-adrenergic antagonists (β-blockers). Renin level was correlated negatively to atrial natriuretic peptide level and the use of b-blockers, and it was elevated above normal levels in subjects using angiotensin converting enzyme inhibitors and diuretics as well as in subjects who had previously suffered myocardial infarction. After exclusion of data for women being administered estrogen replacement therapy, multivariate analysis revealed that sex (P < 0.001), age (P < 0.02), blood pressure (P < 0.002), diabetes (P < 0.05), and the use of angiotensin converting enzyme inhibitors (P < 0.002), β-blockers (P < 0.001), and diuretics (P < 0.05) were independent determinants of plasma prorenin. Plasma renin was independently related to atrial natriuretic peptide level (P < 0.01) and the use of angiotensin converting enzyme inhibitors (P < 0.001), b-blockers (P < 0.001), and diuretics (P < 0.05).

Conclusions These data demonstrate that there is a sexual dimorphism of prorenin levels in humans, suggesting that sex hormones 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 hypertension in smaller populations. Our findings may help to clarify the potential (patho)physiologic functions of prorenin and to identify the factors that influence the constitutive secretion and intracellular processing of this prohormone.

1Department of Pharmacology, Rotterdam, The Netherlands

2Department of Internal Medicine I, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam (COEUR), Rotterdam, The Netherlands

3Institut für Epidemiologie und Sozialmedizin, University of Münster, Münster and GSF Forschungszentrum, Institut für Epidemiologie, Munich-Neuherberg, Germany

4Klinik für Innere Medizin II, University of Regensburg, Regensburg, Germany.

5Correspondence and requests for reprints to A.H.J. Danser, PhD, Department of Pharmacology, Room EE1418b, Erasmus University, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. Tel: +31 10 4087540; fax +31 10 4366839; e-mail danser@farma.fgg.eur.nl

Received 2 July 1997 Revised 30 January 1998 Accepted 3 February 1998

© 1998 Lippincott Williams & Wilkins, Inc.