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)参与脑内多种自主神经反应的调节。本研究利用乌拉坦麻醉大鼠，研究α_1肾上腺素受体的激活是否参与中枢注射N-甲基-D-天冬氨酸诱发的肾上腺髓质内儿茶酚胺外流。下丘脑室旁核灌流NMDA(0.3 mM和1.0 mM)可剂量依赖性地增加下丘脑室旁核去甲肾上腺素水平和血浆儿茶酚胺水平。这些反应可被NMDA受体的选择性非竞争性拮抗剂苹果酸地佐西平(MK-801，0.1 mM)和血栓烷A2受体的选择性竞争性拮抗剂(+)-S-145(2.5 mM)联合应用而取消。这些结果提示，中枢α_1-肾上腺素受体的激活参与了中枢给予N-甲基-D-天冬氨酸所致大鼠肾上腺髓质内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此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.