Aldosterone stimulation by angiotensin II - influence of gender, plasma renin, and familial resemblance

The aldosterone response to infused angiotensin II (Ang II) in patients rec eiving a low-salt diet has been described as an important phenotype for gen etic studies on human hypertension. The objectives of the present study wer e to determine the parameters that influence this intermediate phenotype as a quantitative trait and to assess the importance of its familial resembla nce in hypertensive sibling pairs. Two hundred one white hypertensive subje cts (95 families: 84 pairs and 11 trios) were selected in 3 centers. The pa tients followed the same protocol, which included a 4-week withdrawal perio d 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 great er 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 sibli ng pairs (r=0.11, NS). Conversely, strong sibling correlations were found a mong 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 obtai ned when the Ang I-aldosterone response was analyzed as a qualitative trait (kappa=0.35, P<0.008 in brother-brother pairs). We conclude that age, gend er, 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 associ ation studies.