Effects of an angiotensin converting enzyme inhibitor, ramipril, on intracranial circulation in healthy volunteers. off.
1. The effects of a single oral dose (10 mg) of ramipril on (a) systemic haemodynamics (arterial pressure, cardiac output), (b) carotid artery haemodynamics (blood flow and diameter, pulsed Doppler technique), (c) intracranial haemodynamics (middle cerebral artery mean blood velocity, transcranial Doppler technique), and (d) renin-angiotensin system (plasma converting enzyme and renin activities) have been investigated and compared with those of a placebo during the 24 h period following administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. 2. Ramipril induced a strong and sustained inhibition of plasma converting enzyme activity (-96% at 4 h, -63% at 24 h) and an increase in plasma renin activity (+993% at 8 h). 3. As compared with placebo, ramipril did not significantly affect arterial blood pressure, heart rate, cardiac output and total peripheral resistance. 4. Ramipril significantly increased carotid blood flow (by 27% at 8 h) without significantly changing carotid artery diameter, indicating, given the unchanged arterial pressure, an arteriolar vasodilation in the carotid territory. 5. The middle cerebral artery mean blood flow velocity underwent spontaneous modifications during the placebo period but these changes were not affected by ramipril. This lack of influence of ramipril on intracranial haemodynamics suggests that the drug-induced arteriolar vasodilation and increase in carotid blood flow only concern the extracranial, musculo-cutaneous part of the carotid territory.
Demolis
P
P
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Chalon
S
S
Annane
D
D
Duhaze
P
P
Giudicelli
J F
JF
D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D017257:Ramipril / Q000494:pharmacology*; D012083:Renin / Q000097:blood
D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril