大鼠侧脑室内注射组胺对颈动脉窦压力感受性反射的影响及其中枢机制

Effect of intracerebroventricular injection of histamine on carotid sinus baroreceptor reflex in anesthetized rats and its mechanism

在 5 0只麻醉的大鼠孤离双侧颈动脉窦区 ,将不同窦内压 (ISP)与其对应的平均动脉压 (MAP)值进行Logistic五参数曲线拟合。根据所得ISP MAP关系曲线及其特征参数 ,观察侧脑室注射 (i c v )组胺 (HA)对颈动脉窦压力感受性反射 (CSR)的影响 ,并对其作用机制进行了初步探讨。结果如下 :( 1)i c v HA ( 10 0ng)导致ISP MAP关系曲线显著上移 ,ISP和增益 (Gain)关系曲线中部明显下移 ,反射参数中阈压 (TP)、饱和压 (SP)和最大增益时的窦内压 (ISPGmax)值增大 ,MAP反射变动范围 (MAPrange)及反射最大增益 (Gmax)减小。 ( 2 )预先i c v H1受体拮抗剂氯苯吡胺 (CHL ,5 μg)或H2 受体拮抗剂西咪替丁 (CIM ,15 μg) ,可明显减弱HA的上述效应 ,CIM的这种减弱作用不如CHL的显著。 ( 3 )预先同时i c v CHL和CIM (分别为 5和 15 μg) ,能完全取消HA的效应。 ( 4)预先向孤束核 (NTS)内注射CHL ( 0 5 μg)或CIM ( 1 5 μg) ,对HA效应的影响与i c v CHL或CIM后的相类似 ,但NTS内注射CHL或CIM后i c v HA所致的TP变化表现明显下降。以上结果提示 ,侧脑室给HA使CSR产生快速重调定 ,反射敏感性下降 ,功能受抑 ;其机制是通过中枢HA受体介导 ,H1受体的作用比H2 受体更为明显 ;下丘脑 NTS的HA能通路可能是HA调节CSR的下行通路之?

The changes in carotid sinus baroreceptor reflex (CSR) performance induced by intracerebroventricular injection (i.c.v.) of histamine (HA) were investigated. The effects of pretreatment with HA receptors antagonists into the cerebroventricle or nucleus of solitary tract (NTS) on the responses of CSR to HA were also examined. Intracarotid sinus pressure (ISP)-mean arterial pressure (MAP) relationship curve was constructed by fitting to the logistic function with five parameters in 50 Wistar rats anesthetized with pentobarbital sodium. The left and right carotid sinus regions were isolated from the systemic circulation and the ISP was altered in a stepwise manner. The main results obtained are as follows. (1) i.c.v. injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP-Gain relationship curve downwards, and reduced the MAP range and maximum gain (G max), but increased the threshold pressure (TP), saturation pressure (SP) and ISP at G max (ISP Gmax). (2) The pretreatment with H 1 or H 2 receptors antagonist, chlorpheniramine (CHL, 5 μg) or cimetidine (CIM, 15 μg), could obviously diminish the above-mentioned changes in CSR performance induced by HA, but the effect of CIM was less remarkable than that of CHL. (3) The pretreatment with both CHL and CIM (5 μg and 15 μg) at the same time abolished the responses of CSR performance to HA completely. (4) After microinjection of CHL (0.5 μg) or CIM (1.5 μg) into the NTS, the responses of CSR to HA were similar to those after i.c.v. CHL or CIM, but the change in TP was significantly decreased. These findings suggest that the intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity. The response of CSR to HA might be mediated by both central H 1 and H 2 receptors, especially by H 1 receptors. The effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to NTS. It is suggested that the HA receptors in the NTS play an important role in the responses of CSR to HA.