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


CONCLUSIONS
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.
Demeilliers
B
B
Groupe Rein et Hypertension, Centre Hospitalier Universitaire, Montpellier, France.
Jover
B
B
Mimran
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives; D065168:Bradykinin Receptor Antagonists; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007705:Kinins / Q000502:physiology; D019808:Losartan / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D000804:Angiotensin II; D004656:Enalapril; C065679:icatibant; D012964:Sodium; D019808:Losartan; D001920:Bradykinin