Systemic, regional and cerebral hemodynamic effects of a new angiotensin converting enzyme inhibitor, imidapril, in healthy volunteers.
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.
Démolis
P
P
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Annane
D
D
Duhazé
P
P
Giudicelli
J F
JF
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C065166:imidapril; D012083:Renin