Systemic, regional and cerebral hemodynamic effects of a new angiotensin converting enzyme inhibitor, imidapril, in healthy volunteers

Abstract

The effects of two single oral doses (5 mg and 20 mg) of a new angiotensin I-converting enzyme inhibitor, imidapril, on a) systemic hemodynamics (arterial pressure, heart rate, cardiac output), b) brachial and common carotid arteries' hemodynamics (diameter and blood flow, pulsed Doppler technique), c) cerebral hemodynamics (middle cerebral artery mean blood flow velocity, transcranial Doppler technique), and d) biological parameters (plasma converting enzyme activity, active plasma renin, plasma aldosterone, catecholamines, and atrial natriuretic factor) were investigated and compared with those of a placebo during the 24 h period following administration in a randomized, double-blind, cross-over study performed in six healthy volunteers. Imidapril induced a strong, dose-dependent and sustained inhibition of plasma converting enzyme activity and at the 20 mg an increase in active plasma renin. Other investigated biological parameters were not drug-affected. Imidapril, whatever the dose, did not significantly affect systemic hemodynamic parameters. Imidapril, 20 mg, significantly increased common carotid artery blood flow and diameter and brachial artery diameter. Brachial blood flow also tended to increase but this was not significant. The middle cerebral artery mean blood flow velocity investigated in only five volunteers, underwent spontaneous variations after placebo, and these variations were not affected by imidapril, suggesting that imidapril, whatever the dose, does not influence cerebral blood flow. Thus, imidapril's vasodilating properties apparently affect only the muscular (brachial artery) and cutaneous (external carotid artery) territories, but do not influence the cerebral vascular bed.

Lisinopril improves endothelial function in chronic cigarette smokers

“…Effective renal blood flow increased significantly only in patients treated with spirapril, and not in those treated with captopril, and there were no changes in hepatic blood flow or cerebral blood flow [43]. Others have found no significant increase in brachial artery flow with ACE inhibition [44,45]. It has been documented that an ACE inhibitor can reduce basal and post-exercise limb blood flow in humans [46].…”

Lisinopril improves endothelial function in chronic cigarette smokers

“…Although there is little doubt that, when infused directly into an artery, ACE inhibitors and their precursors cause arteriolar vasodilatation, systemic administration of an ACE inhibitor does not necessarily have the same effect, because a decrease in blood pressure will tend to reduce blood flow while vasodilatation will tend to increase blood flow, i.e. Others have found no significant increase in brachial artery flow with ACE inhibition [44,45]. This may be why oral ACE inhibition did not alter cerebral blood flow in one study [41], but lowered cerebral blood flow in another [42].…”

Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE‐inhibitor imidapril in hypertensive patients

“…Imidapril is an angiotensin converting enzyme (ACE) inhibitor without an SH‐group, currently under investigation for treatment of hypertension and congestive heart failure (CHF) [1–3]. Imidapril is a prodrug, its active metabolite imidaprilat is generated in the liver after hydroxylation and eliminated via the kidneys [4].…”

“…About 40% of the drug is absorbed after oral administration [4]. In healthy volunteers, imidapril, 10 mg once daily, resulted in 85–90% inhibition of plasma ACE [1, 3]. In patients with mild to moderate hypertension the same dose of 10 mg once daily has induced sustained reduction of blood pressure in about 60% of treated patients.…”