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 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.


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 beta-adrenergic antagonists (beta-blockers). Renin level was correlated negatively to atrial natriuretic peptide level and the use of beta-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), beta-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), beta-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.
Danser
A H
AH
Department of Pharmacology, Cardiovasculaire Onderzoeksinstituut Erasmus Universiteit Rotterdam, The Netherlands. danser@farma.fgg.eur.nl
Derkx
F H
FH
Schalekamp
M A
MA
Hense
H W
HW
Riegger
G A
GA
Schunkert
H
H
D000367:Age Factors; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology; D004792:Enzyme Precursors / Q000097:blood* / Q000187:drug effects; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D015592:Immunoradiometric Assay; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D017698:Postmenopause / Q000097:blood / Q000187:drug effects; D015995:Prevalence; D011897:Random Allocation; D012083:Renin / Q000097:blood* / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012189:Retrospective Studies; D012727:Sex Characteristics
D000959:Antihypertensive Agents; D015415:Biomarkers; D004792:Enzyme Precursors; D009320:Atrial Natriuretic Factor; D012083:Renin