Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat.
Chronic hypertension shifts the lower limit of cerebral blood flow autoregulation to a higher pressure level. Although acute administration of angiotensin converting enzyme inhibitors restores the lower limit of cerebral blood flow autoregulation the chronic effects have not received much attention. We studied the effect of the angiotensin converting enzyme inhibitor, perindopril, on mean arterial pressure, basal cerebral blood flow and cerebral blood flow autoregulation in renovascular hypertensive (two-kidney, one clip model) and normotensive male Wistar rats. Seven weeks after renal artery clipping or sham operation rats received daily intraperitoneal injections of perindopril. The dose was increased from 1 to 8 mg/kg over the first 4 weeks until blood pressure was normalized. Chronic renovascular hypertension caused a marked shift in the lower limit of cerebral blood flow autoregulation but did not alter basal cerebral blood flow. Treatment of hypertensive rats with perindopril normalized blood pressure and restored cerebral blood flow autoregulation. Chronic treatment of normotensive rats with perindopril increased basal cerebral blood flow. In conclusion, chronic treatment of renovascular hypertensive rats with perindopril causes a shift in the lower limit of cerebral blood flow autoregulation towards the value observed in normotensive rats.
Muller
F
F
Laboratorie de Pharmacologie, Faculté de Pharmacie, Nancy, France.
Lartaud
I
I
Bray
L
L
Atkinson
J
J
Janian
P
P
Burlet
C
C
Capdeville
C
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D006984:Hypertrophy; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril