Angiotensin-converting enzyme inhibition causes deterioration in renal function in one-kidney Goldblatt hypertensive rats with and without renal arterial stenosis

Abstract

1. The renal and hypotensive effects of a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril, were evaluated in 18 one-kidney, one-clip Goldblatt hypertensive rats (1K1C), 10 one-kidney normotensive rats (1K) and eight 1K1C rats with acute unclipping (1KU). Cilazapril was infused intravenously (25 micrograms/kg per min) into anaesthetized rats, and the arterial blood pressure (BP) and renal clearance of rats were measured. 2. In 1K rats, cilazapril reduced BP from 123 +/- 4 to 117 +/- 4 mmHg (P < 0.05), and produced diuresis, natriuresis and kaliuresis without significantly changing glomerular filtration rate (GFR). 3. In 1K1C rats, cilazapril significantly reduced BP (from 157 +/- 5 to 143 +/- 6 mmHg; P < 0.05), GFR (14.4 +/- 6.7%), urine flow (27.1 +/- 8.5%) and sodium excretion (39.4 +/- 7.4%). Mechanically graded reductions of renal arterial pressure alone also produced parallel decreases in GFR and renal excretory function. 4. In 1KU rats, removal of the renal arterial clip significantly decreased BP and increased renal function. Subsequent infusion of cilazapril further reduced BP and urinary excretions of sodium and water but did not significantly change GFR. 5. These results suggest that the renal function of the 1K1C hypertensive model is pressure-dependent, and that ACE inhibitor exerts a mild antihypertensive effect but causes a pressure associated reduction in renal function. Furthermore, the detrimental effect of ACE inhibitor on the residual kidney persists after acute surgical correction of the stenosis.