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 attenuate the antihypertensive effect of angiotensin II (AngII) type-1 receptor blockade, thus suggesting that nitric oxide might partly mediate the systemic 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 normotensive rats infused or not with NG-nitro-L-arginine methyl ester (L-NAME) (20 microg/kg per min for 60 min). Candesartan was given at a dose of 0.5 mg/kg intravenous bolus in normotensive rats. Candesartan reduced arterial pressure by 15+/-2% and renal vascular resistance by 31+/-2% in nonpretreated rats. Pretreatment by L-NAME did not affect the BP lowering effect of candesartan but blunted by 60 to 100% the renal response to candesartan. Concomitant administration of L-arginine restored the renal vasodilatory action of candesartan. Plasma renin concentration was reduced by L-NAME from 122+/-23 to 69+/-14 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 responses 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 nitric oxide-dependent tone, which participates in the full expression of the renal vasodilatory action of AngII type-1 receptor blockade in anesthetized normotensive rats.
Demeilliers
B
B
Groupe Rein et Hypertension, Faculté de Médecine, Montpellier, France.
Mimran
A
A
Jover
B
B
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester