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 f32 receptor antagonist icatibant (500ptg/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.
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. That is to say the reninangiotensin
plays a role in cyclosporine-induced toxicity in rats on high
sodium diet. |
