NEUROHUMORAL EFFECTS OF RAMIPRIL IN ANGINA-PECTORIS - A DOUBLE-BLIND,PLACEBO-CONTROLLED TRIAL AGAINST ISOSORBIDE DINITRATE AND THE COMBINATION OF RAMIPRIL PLUS ISOSORBIDE DINITRATE

Elevated levels of neurohormones are directly correlated with cardiova scular risk. This double-blind, parallel-group study was designed to e xamine whether treatment with an angiotensin-converting enzyme (ACE) i nhibitor, ramipril, could positively influence the plasma levels of ne urohormones-plasma renin activity (PRA), aldosterone, atrial natriuret ic 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 congest ive heart failure, aged 42 to 72 years (mean, 62.8 years), were enroll ed in four parallel study groups. Test medications were administered a s a single dose in a double-blind, parallel-group manner with a double -dummy technique as follows: ramipril (5 mg), ISDN (20 mg), the combin ation ramipril + ISDN, and placebo. PRA, aldosterone, AL?JP, and endot helin concentrations were estimated before and 1, 2, 3, 4, 6, 8, and 2 4 hours after drug administration. Plasma endothelin levels decreased significantly in the groups receiving ramipril treatment, whereas no c hange was seen after placebo or ISDN administration. No significant ch anges were seen for ANP, whereas PRA increased and aldosterone decreas ed in the groups receiving ramipril. A single dose of ramipril reduced plasma endothelin in patients with angina pectoris, whereas no signif icant changes were observed for ANP. The changes seen with PRA and ald osterone were as expected for ACE inhibitors.