Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats

1 Neurobiology Research Unit, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen; and 2 Department of Nephrology, Herlev Hospital, Copenhagen, Denmark Submitted 10 February 2003 ; accepted in final form 1 May 2003 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 133 Xe 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. renin-angiotensin system; nephrectomy; captopril Address for reprint requests and other correspondence: O. B. Paulson, Neurobiology Research Unit 9201, Rigshospitalet, Copenhagen Univ. Hospital, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark (E-mail: paulson{at}nru.dk ).