Hemodynamic responses to angiotensin I in normal volunteers and the antagonism by the angiotensin-converting enzyme inhibitor cilazapril.

According to classic pharmacologic theory, agonist/antagonist competition can be used to quantify an antagonist's potency by measurement of agonist dose-response curves in the presence of varying doses of the antagonist. We used this principle to characterize the interaction between angiotensin I (AI) and the angiotensin-converting enzyme (ACE) inhibitor cilazapril in humans. In addition, by comparing the effects of AI and angiotensin II before and after administration of a 30-mg dose of cilazapril, we could show the specific AI antagonism of the ACE inhibitor in humans. To obtain the antagonist's dose-response curves, six healthy male volunteers received five single oral doses of cilazapril, 0.5-8.0 mg. Enalapril, 10 mg, and captopril, 12.5 mg, served as positive controls and placebo as the negative control. Dose-response curves following intravenous infusions of AI were established 4 h after oral ingestion of the ACE inhibitors. Noninvasively measured systolic and diastolic blood pressures and total peripheral resistance assessed AI effects. Cilazapril dose dependently shifted the AI dose-response curve rightward, with 1.0 mg inducing a twofold shift. Enalapril and captopril appear less potent, on a milligram basis, in antagonizing AI effects 4 h after drug intake. The methodology could be a useful tool for a rational testing and comparison of ACE inhibitors in clinical pharmacology.