INVOLVEMENT OF NEUROHUMORAL FACTORS IN THE PRESSOR MECHANISM OF N-G-NITRO-L-ARGININE

The mechanism of the N-G-nitro-L-arginine (L-NNA)-induced presser resp onse was examined in pentobarbital-anesthetized dogs. The presser effe ct of L-NNA (50 mg/kg, i.v.) was significantly and equally diminished by pretreatment with either hexamethonium (25 mg/kg, i.v.) or phentola mine (5 mg/kg, i.v.). The intracisternal administration of L-NNA (1 mg /kg), which did not cause changes in cardiovascular parameters when ad ministered systemically, produced a significant presser response and t achycardia. Furthermore, significant suppression of L-NNA-induced pres ser responses was observed after treatment of dogs with captopril (5 m g/kg, i.v.) or a non-peptide angiotensin II receptor antagonist, losar tan (10 mg/kg, i.v.), or bilateral occlusion of renal veins. The inhib itory effects of hexamethonium and losartan were additive. These resul ts suggest that, in addition to vasoconstriction due to the inhibition of endothelial nitric oxide production, increased activity of the sym pathetic nervous and renin-angiotensin systems contributes significant ly to the development of presser responses produced by the intravenous injection of L-NNA in anesthetized dogs.