Regulation of aldosterone secretion in patients with chronic congestive heart failure by endothelins

We studied acute (day 1) and long-term (day 14) effects of endothelin (ET) receptor blockade with the mixed ETA/B antagonist bosentan (1 g twice daily; n = 18) or placebo (n = 12) on plasma angiotensin II and aldosterone in 30 patients with symptomatic chronic heart failure taking angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Hormones were determined before and 3 hours after morning doses of diuretics and digoxin and the double-blind study drug, respectively, on days 1 and 14. On day 1, angiotensin II increased from 16.1 ± 17.9 to 27.6 ± 5.6 ng/L (p <0.05) with bosentan and similarly with placebo (15.5 ± 9.3 and 36.0 ± 49.1 ng/L, p = 0.06) after the morning dose of diuretics and digoxin. Aldosterone tended to increase from 322 ± 239 to 362 ± 254 pmol/L (bosentan) and from 271 ± 70 to 297 ± 136 pmol/L (placebo). On day 14, before drug intake, angiotensin II was unchanged compared with day 1 in both groups. However, aldosterone was lower than on day 1 with bosentan (213 ± 124 vs 322 ± 239 pmol/L, p <0.05) and remained below baseline values 3 hours after drug intake, whereas it was unchanged with placebo. Thus, short-term ETA/B receptor antagonism decreases basal aldosterone secretion independently of angiotensin II, suggesting that ET participates in the regulation of aldosterone in patients already treated with angiotensin-converting enzyme inhibitors and diuretics.