Effects on Autonomic Function of a New Angiotensin Converting Enzyme Inhibitor, Ramipril

Abstract

To investigate the effects of ramipril, a new angiotensin converting enzyme inhibitor, on autonomic function, autonomic function tests were performed in eight healthy male subjects, aged 22–26 years, after single oral administration of 5 mg of ramipril or placebo, in a randomized, double-blind, crossover design. Measurements of heart rate variability and diving reflex test were performed as indices of parasympathetic tone. Forearm isometric exercise (handgrip test) and cold pressor test were carried out to evaluate sympathetic nervous reactivity. Supine systolic blood pressure was decreased significantly after ramipril (F = 11.16, p < 0.01), but diastolic blood pressure was not. Heart rate at rest did not significantly differ between ramipril and placebo. Heart rate variability was significantly increased 120 min after ramipril [5.5 ± 0.7% (SEM) on ramipril and 3.7 ± 0.2% on placebo; F = 7.13, p < 0.05]. However, reflex bradycardia during the diving test was not enhanced after ramipril. Plasma norepinephrine concentrations before and after handgrip test were not influenced by ramipril. Increments of mean blood pressure and heart rate during handgrip or cold pressor test did not significantly differ between ramipril and placebo, either. These results suggest that ramipril may enhance cardiac vagal tone without affecting sympathetic nervous activity. Enhanced parasympathetic activity could be related to an absence of reflex tachycardia following the administration of ramipril.