Neurohumoral effects of ramipril in angina pectoris: A double-blind, placebo-controlled trial against isosorbide dinitrate and the combination of ramipril plus isosorbide dinitrate

Abstract

Elevated levels of neurohormones are directly correlated with cardiovascular risk. This double-blind, parallel-group study was designed to examine whether treatment with an angiotensin-converting enzyme (ACE) inhibitor, ramipril, could positively influence the plasma levels of neurohormones—plasma renin activity (PRA), aldosterone, atrial natriuretic peptide (ANP), and endothelin—and whether differences exist between treatments with ramipril, isosorbide dinitrate (ISDN) alone, ramipril + ISDN or placebo. Thirty-two patients (1 woman, 31 men) with congestive heart failure, aged 42 to 72 years (mean, 62.8 years), were enrolled in four parallel study groups. Test medications were administered as a single dose in a double-blind, parallel-group manner with a double-dummy technique as follows: ramipril (5 mg), ISDN (20 mg), the combination ramipril + ISDN, and placebo. PRA, aldosterone, ANP, and endothelin concentrations were estimated before and 1, 2, 3, 4, 6, 8, and 24 hours after drug administration. Plasma endothelin levels decreased significantly in the groups receiving ramipril treatment, whereas no change was seen after placebo or ISDN administration. No significant changes were seen for ANP, whereas PRA increased and aldosterone decreased in the groups receiving ramipril. A single dose of ramipril reduced plasma endothelin in patients with angina pectoris, whereas no significant changes were observed for ANP. The changes seen with PRA and aldosterone were as expected for ACE inhibitors.