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 3 0 patients with symptomatic chronic heart failure faking angiotensin-conver ting enzyme inhibitors, diuretics, and digoxin. Hormones were determined be fore and 3 hours after morning doses of diuretics and digoxin and the doubl e-blind study drug, respectively, on days 1 and 14, On day 1, angiotensin I t 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 inc rease 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, angiotensi n 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, wher eas it was unchanged with placebo. Thus, shortterm ETA/B receptor antagonis m decreases basal aldosterone secretion independently of angiotensin II, su ggesting that PT participates in the regulation of aldosterone in patients already treated with angiotensin-converting enzyme inhibitors and diuretics . (C) 2000 by Excerpta Medica, Inc.