Thromboxane A2 is involved in the nitric oxide-induced central activation of adrenomedullary outflow in rats

The central effect of 3-morpholinosydnonimine, a nitric oxide donor, on the sympathoadrenomedullary system was investigated in urethane-anesthetized rats. Intracerebroventricular administration of 3-morpholinosydnonimine (100, 250 and 500 mu g/animal) induced a marked elevation of adrenaline levels and a slight elevation of noradrenaline levels in the plasma. These 3-morpholinosydnonimine (250 mu g/animal)-induced elevations of catecholamines were abolished by intracerebroventricular treatments with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (750 mu g/animal), a nitric oxide scavenger, and indomethacin (500 mu g/animal), a cyclo-oxygenase inhibitor, but not with superoxide dismutase (250 units/animal), a superoxide anion scavenger. Furthermore, the 3-morpholinosydnonimine (250 mu g/animal)-induced elevation of plasma adrenaline levels was abolished by intracerebroventricular treatments with thromboxane A(2) synthase inhibitors [furegrelate (100, 250 and 1000 mu g/animal) and carboxyheptyl imidazole (500 mu g/animal)], and also with thromboxane A(2) receptor blockers [(+)-S-145 (100, 250 and 1000 mu g/animal) and SQ29548 (8 mu g/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. (C) 1998 IBRO. Published by Elsevier Science Ltd.