CAPTOPRIL DOES NOT ACUTELY MODULATE PLASMA ENDOTHELIN-1 CONCENTRATIONIN HUMAN CONGESTIVE-HEART-FAILURE

Congestive heart failure (CHF) is a syndrome characterized by increase d levels of angiotensin II (Ang II) and endothelin-1 (ET-1). In vitro, Ang II stimulates ET-1 release. The purpose of this study was to asse ss the effect of a single dose of an angiotensin-converting enzyme inh ibitor (ACEI) captopril versus placebo on plasma endothelin concentrat ion in human congestive heart failure. Captopril (25 mg, given orally) was compared with placebo in a group of 20 patients with systolic dys function in a double-blind randomized study. Plasma irET concentration was significantly increased in CHF patients compared with normal subj ects (5.59 pg/ml +/- 0.35 vs. 3.58 pg/ml +/- 0.99, p < 0.0002). Despit e the decrease in systolic blood pressure and the increase in plasma r enin activity, suggesting a significant blockade of the renin-angioten sin system, no difference in plasma irET-1 was observed between captop ril and placebo. Our results suggest that captopril does not acutely i nfluence irET-1 plasma concentration in human CHF. These data do not s upport the hypothesis that the acute vasodilator effect of a single do se of 25 mg of captopril given orally involves modulation of the incre ased plasma concentration of endothelin observed in CHF.