Bilateral renal function responses to converting enzyme inhibitor (SQ 20,881) in two-kidney, one clip Goldblatt hypertensive rats.

Abstract

The influence of the renin-angiotensin system on individual kidney function of 2-kidney, 1 clip Goldblatt hypertensive (GH) rats was evaluated by determining renal functional responses during i.v. infusion of converting enzyme inhibitor (CEI) (SQ 20,881 [teprotide], 0.3 mg/100 g .cntdot. h) for 3.5 h. Rats were made hypertensive by placing a 0.25 mm silver clip on the right renal artery 3-4 wk prior to study. Normal rats and GH rats were prepared to allow urine collections from each kidney. Mean arterial pressure of GH rats fell significantly from preinfusion levels of 153 .+-. 7 to 126 .+-. 4 mm Hg during CEI infusion. Despite this decrease in arterial pressure, the nonclipped kidneys with reduced renal renin activity (14 .+-. 15 vs. 293 .+-. 40 ng AI/mg .cntdot. h in the clipped kidney) exhibited dramatic increases in glomerular filtration rate (GFR) (from 1.45 .+-. 0.06 to 2.56 .+-. 0.35 ml/min), urine flow (4.82 .+-. 0.71 to 9.11 .+-. 1.19 .mu.l/min), Na excretion (0.10 .+-. 0.02 to 1.15 .+-. 0.39 .mu.eq/min), fractional Na excretion (0.05% .+-. 0.02% to 0.43% .+-. 0.18%), and K excretion (0.94 .+-. 0.08 to 2.50 .+-. 0.55 .mu.eq/min). Significant arterial-pressure-associated decreases in GFR, urine flow and salt excretion were observed in the clipped kidney. In normal rats, CEI infusion produced reduction in arterial pressure and increases in GFR, urine flow and Na excretion that were of smaller magnitude than those observed in the nonclipped kidneys of GH rats. Plasma renin activity was significantly higher in GH rats than in normal rats (24.0 .+-. 2.7 vs. 12.8 .+-. 3.4 ng Al/ml.cntdot.h). The augmented renal responses to CEI by the nonclipped kidney suggest that elevated circulating angiotensin levels exert a substantial influence on hemodynamic and excretory function of these kidneys even though intrarenal renin activity is markedly reduced. This influence may led to fluid and electrolyte retention and may partially explain the apparent failure of the nonclipped kidney to prevent the development of hypertension.