RELATION BETWEEN L-ARGININE-NITRIC OXIDE PATHWAY AND ENDOTHELIN-1 EFFECTS IN PERIAQUEDUCTAL GRAY AREA OF RATS

Injection of N-omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (FAG) area of freely moving rats at doses from 0.1 to 1 mu mol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced presser effects. Administration of L-NAME (1 mu mol per rat) in the FAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mu mol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 presser effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME presser effects. Our data suggest the presence of NO synthase in the FAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the FAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.