CONTRASTING RENAL EFFECTS OF CHRONIC ADMINISTRATIONS OF ENALAPRIL ANDLOSARTAN ON ONE-KIDNEY, ONE-CLIP HYPERTENSIVE RATS

Objective To compare the effects of chronic administrations of the ang iotensin II antagonist losartan and of the angiotensin I converting en zyme inhibitor enalapril on renal function in sodium-depleted rats wit h one-kidney, one clip hypertension, and to examine the contribution o f endogenous kinins to the effect of enalapril. Methods We administere d enalapril and losartan (10 and 30 mg/kg per day, respectively) for 6 days to hypertensive rats that had been subjected to dietary sodium-i ntake restriction for 6 days prior to treatment and continued to be su bjected to this restriction during treatment In an additional group, a dministration of enalapril was combined with infusion of the bradykini n B-2-receptor antagonist Hoe 140 (300 mu g/kg per day subcutaneously via an osmotic pump). Renal function of anesthetized rats was assessed by using a clearance technique, Results Despite there being similar f alls in arterial pressure, glomerular filtration rate (867 +/- 40 mu l /min per g kidney weight in untreated rats) was decreased to a larger extent in enalapril-treated than it was in losartan-treated rats (284 +/- 29 versus 438 +/- 36 mu l/min per g kidney weight, P< 0.01). Altho ugh infusion of Hoe 140 had no influence on the effect of enalapril on arterial pressure, the level of glomerular filtration achieved in rat s of this group (545 +/- 55 mu l/min per g kidney weight) was similar to that found in losartan-treated rats.. No effect of either treatment on renal plasma flow was detected; as a consequence, the excessive de crease in filtration fraction observed for rats in the enalapril-treat ed group was corrected by concomitant administration of Hoe 140. Inter estingly, administration of enalapril resulted in a greater loss of so dium than did administration of losartan (723 +/- 147 versus 308 +/- 5 7 mu mol during 6 days), and this effect was abolished by infusion of Hoe 140 (353 +/- 42 mu mol during 6 days). Conclusion Administration o f enalapril to sodium-depleted rats with one-kidney, one clip hyperten sion reduces their glomerular filtration rate to a greater extent than does administration of losartan despite these agents having similar e ffects on systemic blood pressure. Combined administration of enalapri l and Hoe 140 has a less marked effect on glomerular filtration rate t han does that of enalapril alone, This suggests that kinins play a rol e in the regulation of efferent arteriolar tone in this rat model. I H ypertens 16:1023-1029 (C) 1998 Lippincott-Raven Publishers.