Contrasting renal effects of chronic administrations of enalapril and losartan on one-kidney, one clip hypertensive rats.

摘要

OBJECTIVE: To compare the effects of chronic administrations of the angiotensin II antagonist losartan and of the angiotensin I converting enzyme inhibitor enalapril on renal function in sodium-depleted rats with one-kidney, one clip hypertension, and to examine the contribution of endogenous kinins to the effect of enalapril. METHODS: We administered enalapril and losartan (10 and 30 mg/kg per day, respectively) for 6 days to hypertensive rats that had been subjected to dietary sodium-intake restriction for 6 days prior to treatment and continued to be subjected to this restriction during treatment. In an additional group, administration of enalapril was combined with infusion of the bradykinin B2-receptor antagonist Hoe 140 (300 microg/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 falls in arterial pressure, glomerular filtration rate (867 +/- 40 microl/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 microl/min per g kidney weight, P < 0.01). Although infusion of Hoe 140 had no influence on the effect of enalapril on arterial pressure, the level of glomerular filtration achieved in rats of this group (545 +/- 55 microl/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 decrease in filtration fraction observed for rats in the enalapril-treated group was corrected by concomitant administration of Hoe 140. Interestingly, administration of enalapril resulted in a greater loss of sodium than did administration of losartan (723 +/- 147 versus 308 +/- 57 micromol during 6 days), and this effect was abolished by infusion of Hoe 140 (353 +/- 42 micromol during 6 days). CONCLUSION: Administration of enalapril to sodium-depleted rats with one-kidney, one clip hypertension reduces their glomerular filtration rate to a greater extent than does administration of losartan despite these agents having similar effects on systemic blood pressure. Combined administration of enalapril and Hoe 140 has a less marked effect on glomerular filtration rate than does that of enalapril alone. This suggests that kinins play a role in the regulation of efferent arteriolar tone in this rat model.