Nitric oxide participates in the renal vasodilatory effect of candesartan in anesthetized rats

Inhibition of nitric oxide synthase by L-arginine analogues was shown to at tenuate the antihypertensive effect of angiotensin II (AngII) type-1 recept or blockade, thus suggesting that nitric oxide might partly mediate the sys temic effect of these agents. In the present experiment, the effects of an acute administration of candesartan on arterial pressure, renal blood flow (transit time method), and resistance were assessed in anesthetized normote nsive rats infused or not with N-G-nitro-L-arginine methyl ester (L-NAME) ( 20 mu g/kg per min for 60 min). Candesartan was given at a dose of 0.5 mg/k g intravenous bolus in normotensive rats. Candesartan reduced arterial pres sure by 15 +/- 2% and renal vascular resistance by 31 +/- 2% in nonpretreat ed rats. Pretreatment by L-NAME did not affect the BP lowering effect of ca ndesartan but blunted by 60 to 100% the renal response to candesartan, Conc omitant administration of L-arginine restored the renal vasodilatory action of candesartan. Plasma renin concentration was reduced by L-NAME from 122 +/- 23 to 69 +/- 13 ng AngI/ml per h and not further modified by L-arginine (71 +/- 16 ng AngI/ml per h). Neither the systemic and renal hemodynamic r esponses to AngII nor its blockade by candesartan were affected by L-NAME. The loss of renal vasodilatory effect of candesartan during L-NAME infusion suggests that AT1 receptor blockade is associated with an increase in nitr ic oxide-dependent tone, which participates in the full expression of the r enal vasodilatory action of AngII type-1 receptor blockade in anesthetized normotensive rats.