Alpha1-adrenoceptor activation is involved in the central N-methyl-D-aspartate-induced adrenomedullary outflow in rats.

N-methyl-D-aspartate (NMDA) has been implicated in the regulation of several autonomic responses in the brain. The present study determined whether activation of alpha1-adrenoceptors is involved in the centrally administered NMDA-induced adrenomedullary catecholamine outflow, using urethane-anesthetized rats. The NMDA (5.0 nmol/animal, i.c.v.)-induced elevation of plasma levels of noradrenaline and adrenaline was reduced by phentolamine (0.33 micromol/animal, i.c.v.), a non-selective alpha-adrenoceptor antagonist, and by 2-{[b-(4-hydroxyphenyl)ethyl]aminomethyl}-1 tetralone (HEAT) (90.0 nmol/animal, i.c.v.), a selective alpha1-adrenoceptor antagonist. In contrast, sotalol (0.8 micromol/animal, i.c.v.), a non-selective beta-adrenoceptor antagonist, did not alter the responses. In addition, U-73122, a phospholipase C inhibitor (5.0 nmol/animal, i.c.v.), RHC-80267, a diacylglycerol lipase inhibitor (1.3 micromol/animal, i.c.v.) and URB 602, a monoacylglycerol lipase inhibitor (0.85 and 1.7 micromol/animal, i.c.v.), reduced the NMDA-induced plasma elevation of both catecholamines. Furthermore, perfusion of the hypothalamic paraventricular nucleus with NMDA (0.3 and 1.0 mM) dose-dependently elevated both noradrenaline levels in the hypothalamic paraventricular nucleus and plasma catecholamine levels. These responses were abolished by co-administration of dizocilpine malate (MK-801, 0.1 mM), a selective non-competitive antagonist of the NMDA receptor and by co-administration of (+)-S-145 (2.5 mM), a selective competitive antagonist of the thromboxane A2 receptor. These results suggest that activation of central alpha1-adrenoceptors is involved in the centrally administered NMDA-induced activation of adrenomedullary catecholamine outflow in rats. Furthermore, signaling cascades downstream of the alpha1-adrenoceptor in the hypothalamic paraventricular nucleus may play an important role in the process.