Abstract The central effect of 3-morpholinosydnonimine, a nitric oxide donor, on the sympatho-adrenomedullary system was investigated in urethane-anesthetized rats. Intracerebroventricular administration of 3-morpholinosydnonimine (100, 250 and 500 μg/animal) induced a marked elevation of adrenaline levels and a slight elevation of noradrenaline levels in the plasma. These 3-morpholinosydnonimine (250 μg/animal)-induced elevations of catecholamines were abolished by intracerebroventricular treatments with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (750 μg/animal), a nitric oxide scavenger, and indomethacin (500 μg/animal), a cyclo-oxygenase inhibitor, but not with superoxide dismutase (250 units/animal), a superoxide anion scavenger. Furthermore, the 3-morpholinosydnonimine (250 μg/animal)-induced elevation of plasma adrenaline levels was abolished by intracerebroventricular treatments with thromboxane A 2 synthase inhibitors [furegrelate (100, 250 and 1000 μg/animal) and carboxyheptyl imidazole (500 μg/animal)], and also with thromboxane A 2 receptor blockers [(+)-S-145 (100, 250 and 1000 μg/animal) and SQ29548 (8 μg/animal)]. The elevation of noradrenaline levels was, however, not attenuated by these thromboxane A 2-related test agents. The present results indicate that nitric oxide but not peroxynitrite markedly activates central adrenomedullary outflow. Thromboxane A 2 in the brain is probably involved in this central activation of adrenomedullary outflow.