Non‐contribution of renin‐angiotensin system to pressor response to NG‐nitro‐L‐arginine in dogs

Acute systemic blockade of nitric oxide (NO) production by nonselective inhibitors of NO synthase (NOS) isoforms, including N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA), has been shown to produce a long-lasting pressor response in conscious and anaesthetised animals. The present study was undertaken to clarify whether the renin-angiotensin system contributes to the development of this pressor response to L-NNA. Systemic blood pressure and heart rate were continuously monitored in dogs anaesthetised with pentobarbital. Plasma renin activity in the blood obtained from a femoral artery and a renal vein was measured by use of radioimmunoassay. The acute pressor response produced by the intravenous administration of L-NNA was accompanied by reduced renin activity in both systemic and renal vascular beds. Captopril, an angiotensin converting enzyme inhibitor, counteracted the pressor response to L-NNA, whereas candesartan, an angiotensin AT1-receptor antagonist, had no apparent effect on it. The counteraction by captopril of the L-NNA-induced pressor response was likely to be attributable to enhancement by captopril of depressor responses to bradykinin, as HOE-140, a bradykinin B2 receptor antagonist, neutralised the effect of captopril. These results suggest that the pressor response acutely produced by the intravenous injection of a NOS inhibitor is not mediated by the renin-angiotensin system in anaesthetised dogs.