Effects of Saralasin Infusion on Bilateral Renal Function in Two-Kidney, One-Clip Goldblatt Hypertensive Rats

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Abstract
1. Previous studies have shown that administration of converting enzyme inhibitor (CEI, SQ 20 881) to two-kidney, one-clip Goldblatt hypertensive (GH) rats clipped for 3–4 weeks resulted in marked increases in glomerular filtration rate (GFR), water and sodium excretion by the non-clipped kidneys. The clipped kidneys exhibited reduced function that was due, in part, to the reductions in arterial pressure. To evaluate further the hypothesis that the renal responses to CEI were due primarily to the inhibition of angiotensin II rather than other factors, we infused the angiotensin II competitive blocker, saralasin, into GH rats under sodium pentobarbital anaesthesia and examined renal haemodynamics and excretory function of each kidney before and during saralasin infusion and after cessation of saralasin infusion. 2. Saralasin reduced mean arterial blood pressure from 164 ± 4 to 124 ± 4 mmHg. Despite the profound fall of arterial pressure, significant increases in renal blood flow from 5.82 ± 0.22 to 9.15 ± 0.76 ml/min and glomerular filtration rate from 1.46 ± 0.10 to 2.18 ± 0.14 ml/min were observed in the non-clipped kidneys. Renal vascular resistance decreased from 2.34 (± 0.14) × 105 to 1.17 (± 0.19) × 105 kPa l−1 s [2.34 (± 0.14) × 106 to 1.17 (± 0.19) × 106 dyn s cm−5]. Also, concomitant diuresis and kaliuresis and a delayed natriuresis occurred. Correspondence: Dr L. G. Navar, University of Alabama in Birmingham Medical Center, University Station, 727 CDLD Bldg, Birmingham, Alabama 35294, U.S.A. 3. The clipped kidneys exhibited reductions in renal blood flow, GFR and excretory function during saralasin infusion. 4. Normal rats receiving the identical dose of saralasin responded with a slight but significant decrease in arterial pressure. The increases in renal blood flow and GFR were less than those observed in the non-clipped kidneys of hypertensive rats. 5. These data provide further support to the hypothesis that an angiotensin II-mediated elevation in renal vascular resistance and impairment of renal function exist in the non-clipped kidneys of GH rats.