In this work, we compared the effects of the angiotensin converting
enzyme inhibitor enalapril and the angiotensin ATI receptor antagonist
valsartan in cyclosporine induced hypertension and nephrotoxicity in rats
on high sodium diet.
Rats on high sodium diet for 6 weeks, were given cyclosporine
(5mg/kg/day S.C). The rats were treated concomitantly either with
enalapril (30 mg/kg/day orally) or valsartan (3 or 30 mg/kg/day orally).
To evaluate the role of bradykinin in the action of enalapril, some
rats received a bradykinin P2 receptor antagonist icatibant (500μg/kg/day
S.C) during the last 2 weeks of enalapril treatment.
Blood pressure was recorded every second week by tail cuff
method, renal function was measured by serum creatinine, creatinine
clearance and urinary excretion of proteins at the end of the experiment.
In this study Cyclosporine-caused hypertension, impaired renal
function and induced morphological nephrotoxicity with glomerular
damage and interstitial fibrosis. Enalapril and the lower dose of valsartan
attenuated the cyclosporine-induced hypertension to the same extent,
while the higher dose of valsartan totally abolished it. Icatibant did not
reduce the antihypertensive effect of enalapril.
Enalapril and valsartan equally prevented the cyclosporine-induced
deterioration of kidney function and morphology. From this study we can
conclude that, the renin-angiotensin plays a crucial role in cyclosporineinduced
toxicity in rats on high sodium diet.
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