CENTRAL CIRCUITRY OF AUTONOMIC RESPONSES TO HEMORRHAGE

急性失血会产生一系列生理反应， 帮助恢复心血管内环境平衡。这些是补偿性的 反应包括血管收缩和心输出量增加 部分是由交感神经的刺激引起的。 然而，超过临界水平的失血似乎是自相矛盾的 自动补偿发生逆转，导致戏剧性的 动脉压下降。失代偿期的出血 反应与一些交感神经的抑制和 外周血管阻力的降低。失血所致 交感神经抑制是由心脏迷走神经的激活触发的 投射到孤束核(NTS)的传入纤维 这种反应背后的核心机制仍不清楚。出血- 诱发的交感神经抑制可能是通过抑制神经元在 延髓头端腹外侧区(RVLm) 对交感血管收缩神经的紧张性兴奋性冲动。几个 NTS的传入也触发的反射抑制交感神经 血管舒缩张力(如压力感受器反射和Bexold-Jarish反射) GABA兴奋抑制RVLM前交感神经元 延髓尾侧腹外侧(CVLM)的投射。但是，在 与这些其他反射相比，中枢作用的阿片类药物似乎 对失血引起的交感神经抑制至关重要。阿片受体阻滞剂 中枢而不是外周可以逆转失血 交感神经抑制，但阿片剂背后的中枢机制 对这一反应的贡献尚不清楚。因为鸦片类药物可以抑制 RVLM直接交感前神经元，失血引起交感神经抑制 可能是通过向RVLM释放阿片类药物而发生的，这种释放不依赖于 V|CVLM的抑制性投射。此应用程序有两个目标：1) 为了揭示失血引起的症状抑制的中枢回路， 2)确定阿片肽在这一过程中的作用。

Acute blood loss produces a constellation of physiological responses that aid in the restoration of cardiovascular homeostasis. These compensatory responses include increased constriction of blood vessel and cardiac output brought about, in part, by a stimulation of the sympathetic nervous. However, beyond a critical level of blood loss a seemingly paradoxical reversal of the automatic compensations occurs, leading to a dramatic decrease in arterial pressure. This decompensatory phase of the hemorrhage response is associated with an inhibition of some sympathetic nerves and a decrease in peripheral vascular resistance. Hemorrhage-induced sympathoinhibition is triggered by the activation of cardiac vagal afferents that project to the nucleus tractus solitarius (NTS), but the central mechanism underlying this response remains unknown. Hemorrhage- induced sympahtoinhibition may be produced by a inhibition of neurons in the rostral ventrolateral medulla (RVLM) that provide the major source of tonic excitatory drive to sympathetic vasoconstrictor nerves. Several reflexes that are also triggered by afferents to NTS inhibit sympathetic vasomotor tone (e.g. baroreceptor reflex and Bexold-Jarish reflex)by inhibiting RVLM presympathetic neurons via the excitation of a GABAerigic projection from the caudal ventrolateral medulla (CVLM). However, in contrast to these other reflexes, centrally-acting opiates appears to be crucial for hemorrage-induced sympathoinhibition.. Opiate receptor blockade centrally but not peripherally can reverse hemorrhage-induced sympathoinhibition, but the central mechanism underlying the opiate contribution to this response is not known. Because opiates can inhibit RVLM presympathetic neurons directly, hemorrhage-induced sympathoinhibition may occur by a release of opiates into RVLM that is independent of an inhibilitory projection from V|CVLM. This application has two goals: 1) to reveal the central circuitry for hemorrhage-induced symphathoinhibition, and 2) to determine the role of opiate peptides in this process.