Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats.
The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensin-converting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 +/- 4 mmHg) and sham-operated (58 +/- 4 mmHg) rats compared with diet control rats (78 +/- 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 +/- 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls.
Neurobiology Research Unit 9201, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
Trine Fischer
TF
Pedersen
Olaf B
OB
Paulson
Arne Høj
AH
Nielsen
Svend
S
Strandgaard
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009392:Nephrectomy; D010530:Peritoneal Dialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D002216:Captopril