Role of alpha1 adrenoceptor activation in the hypothalamic paraventricular nucleus on the adrenomedullary outflow in rats

n -甲基- d -天冬氨酸（NMDA）已被认为与大脑中几种自主神经反应的调节有关。本研究用氨基脲麻醉大鼠，确定α_1-肾上腺素受体的激活是否参与中央给药nmda诱导的肾上腺髓质儿茶酚胺流出。下丘脑室旁核灌注NMDA（0.3和1.0mM）剂量依赖性升高下丘脑室旁核去甲肾上腺素水平和血浆儿茶酚胺水平。同时给予苹果酸二唑西平（MK-801, 0.1mM），一种NMDA受体的选择性非竞争性拮抗剂和(+)-S-145 (2.5mM)，一种血栓素A2受体的选择性竞争性拮抗剂，可以消除这些反应。这些结果表明，中枢α_1-肾上腺素受体的激活参与了nmda诱导的大鼠肾上腺髓质儿茶酚胺流出的激活。此外，下丘脑室旁核α_1-肾上腺素能受体下游的信号级联可能在这一过程中发挥重要作用。

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 α_1-adrenoceptors is involved in the centrally administered NMDA-induced adrenomedullary catecholamine outflow, using urethane-anesthetized rats. Perfusion of the hypothalamic paraventricular nucleus with NMDA (0.3 and 1.0mM) 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, 0.1mM), a selective non-competitive antagonist of the NMDA receptor and by co-administration of (+)-S-145 (2.5mM), a selective competitive antagonist of the thromboxane A2 receptor. These results suggest that activation of central α_1-adrenoceptors is involved in the centrally administered NMDA-induced activation of adrenomedullary catecholamine outflow in rats. Furthermore, signaling cascades downstream of the α_1-adrenoceptor in the hypothalamic paraventricular nucleus may play an important role in the process.