Chronic angiotensin converting enzyme inhibition in the two-kidney, one clip hypertensive rat

Treatment with an angiotensin converting enzyme (ACE) inhibitor in renovascular hypertension produces acute effects on renal function; however, the long-term consequences of this are not known. We have studied the effect of chronic enalapril treatment on renal structure and function in the two-kidney, one clip model of renovascular hypertension in the rat. Four weeks after the left renal artery was clipped, the hypertensive rats were randomly allocated to treatment with enalapril, minoxidil or to no treatment. The drug dose was titrated for maximal hypotensive effect. After 4 months of treatment blood pressures were 129 +/- 3 mmHg (enalapril), 193 +/- 5 mmHg (minoxidil) and 220 +/- 4.8 mmHg (no treatment). Twelve months later survival was 84% (enalapril group), 48% (minoxidil group) and 15% (untreated group). Split kidney function (51Cr-EDTA clearance, ml/min) of the clipped kidneys was 0.0 (enalapril group), 0.26 +/- 0.23 (minoxidil group) and 0.74 +/- 0.13 (untreated group). The clipped kidney from enalapril-treated rats weighed 0.46 +/- 0.1 g, much less than in the minoxidil-treated group (1.2 +/- 0.07) or the untreated group (1.14 +/- 0.10). Enalapril treatment was withdrawn for 2 weeks in five rats, but the clipped kidney remained small and non-functional. Histological examination revealed marked interstitial fibrosis and tubular atrophy in clipped kidneys from both enalapril groups, in contrast to minor changes in the minoxidil-treated and the untreated groups. We conclude that chronic enalapril treatment of two-kidney, one clip hypertension in the rat improved survival and preserved total renal function, but was associated with irreversible fibrotic atrophy of the clipped kidney.