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(Hypertension. 2000;35:710.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Aldosterone Stimulation by Angiotensin II

Influence of Gender, Plasma Renin, and Familial Resemblance

Mara Giacché; Albert Vuagnat; Steven C. Hunt; Paul N. Hopkins; Naomi D. L. Fisher; Michel Azizi; Pierre Corvol; Gordon H. Williams; Xavier Jeunemaitre

From the Department of Hypertension (M.G., A.V., M.A., P.C., X.J.), Centre d’Investigation Clinique 9201 AP-HP/INSERM, Hôpital Broussais, and INSERM U36, College de France, Paris, France; Department of Medicine (S.C.H., P.N.H.), University of Utah, Salt Lake City; and Endocrine-Hypertension Division (N.D.L.F., G.H.W.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Dr Xavier Jeunemaitre, INSERM U 36, College de France, 3 rue d’Ulm, 75005 Paris, France. E-mail xavier.jeunemaitre{at}brs.ap-hop-paris.fr

Abstract—The aldosterone response to infused angiotensin II (Ang II) in patients receiving a low-salt diet has been described as an important phenotype for genetic studies on human hypertension. The objectives of the present study were to determine the parameters that influence this intermediate phenotype as a quantitative trait and to assess the importance of its familial resemblance in hypertensive sibling pairs. Two hundred one white hypertensive subjects (95 families: 84 pairs and 11 trios) were selected in 3 centers. The patients followed the same protocol, which included a 4-week withdrawal period of antihypertensive therapy, a 1-week period on a low-salt diet, and a 30-minute infusion of Ang II. The increase in the aldosterone level was greater in women than in men (29.1±16.2 versus 18.2±9.6 ng/dL, P<0.0001). A strong relationship was found with age (r=-0.54, P<10^-4) and plasma renin activity (r=0.32, P<10^-4) in women but not in men. Weak correlations of the aldosterone response to Ang II were observed for the whole set of sibling pairs (r=0.11, NS). Conversely, strong sibling correlations were found among brother-brother pairs (r=0.40, n=36) and among sister-sister pairs as soon as age or menopausal status was considered. Similar results were obtained when the Ang I–aldosterone response was analyzed as a qualitative trait (=0.35, P<0.008 in brother-brother pairs). We conclude that age, gender, and plasma renin are strong determinants of the aldosterone response to Ang II, with strong sibling correlations in men and postmenopausal women. These relationships will have to be considered in future linkage and association studies.

Key Words: hypertension, arterial • genetics • renin-angiotensin system • aldosterone • age • gender

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