Nitric oxide is an excitatory modulator in the rostral ventrolateral medulla in rats

Nitric oxide is a messenger molecule having Various functions in the brain. Previous studies have reported conflicting results for the roles of nitric oxide in the rostral ventrolateral medulla, a major center that regulates sympathetic and cardiovascular activities. We hypothesized that in this reg ion, nitric oxide may have a biphasic effect on cardiovascular activity. Mi croinjection of a low dose (1 nmol) of a nitric oxide donor sodium nitropru sside or a cyclic GMP agonist 8-bromocyclic GMP into this area increased ar terial pressure, whereas injection of a nitric oxide synthase inhibitor N-o mega-nitro-L-arginine methyl ester or a soluble guanylate cyclase inhibitor methylene blue decreased arterial pressure. Microinjection of a high dose (100 nmol) of sodium nitroprusside decreased arterial pressure and inhibite d spontaneous respiration with concomitant production of peroxynitrite, a s trong cytotoxic oxidant. Increases in arterial pressure caused by microinje ction of L-glutamate were inhibited after preinjection of N-omega-nitro-L-a rginine methyl ester or methylene blue. Increases in arterial pressure caus ed by microinjection of sodium nitroprusside (1 nmol) were inhibited after preinjection of a glutamate receptor antagonist kynurenate. These results s uggest that low doses of nitric oxide may increase arterial pressure, where as high doses of nitric oxide may decrease arterial pressure through cytoto xic effects in the rostral ventrolateral medulla. They also indicate that n itric oxide may stimulate neurons both through activation of the nitric oxi de cyclic GMP pathway and through modulation of glutamate receptor stimulat ion, and therefore, increase arterial pressure in rats. Am J Hypertens 2000 ;13:1125-1134 (C) 2000 American Journal of Hypertension, Ltd.