Involvement of neurohumoral factors in the pressor mechanism of NG-nitro-L-arginine.

The mechanism of the NG-nitro-L-arginine (L-NNA)-induced pressor response was examined in pentobarbital-anesthetized dogs. The pressor effect of L-NNA (50 mg/kg, i.v.) was significantly and equally diminished by pretreatment with either hexamethonium (25 mg/kg, i.v.) or phentolamine (5 mg/kg, i.v.). The intracisternal administration of L-NNA (1 mg/kg), which did not cause changes in cardiovascular parameters when administered systemically, produced a significant pressor response and tachycardia. Furthermore, significant suppression of L-NNA-induced pressor responses was observed after treatment of dogs with captopril (5 mg/kg, i.v.) or a non-peptide angiotensin II receptor antagonist, losartan (10 mg/kg, i.v.), or bilateral occlusion of renal veins. The inhibitory effects of hexamethonium and losartan were additive. These results suggest that, in addition to vasoconstriction due to the inhibition of endothelial nitric oxide production, increased activity of the sympathetic nervous and renin-angiotensin systems contributes significantly to the development of pressor responses produced by the intravenous injection of L-NNA in anesthetized dogs.