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孤束核胆碱能与组胺能系统对颈动脉窦压力感受器反射调节的交互作用

胡力旬, 张国兴, 张玉英, 赵红芬, 于康英, 王国卿^*

苏州大学医学部基础医学与生物科学学院生理学系，苏州 215123

摘要

脑胆碱能系统与组胺能系统影响颈动脉窦压力感受器反射(carotid sinus baroreceptor reflex, CSR)活动，然而二者是否在孤束核(nucleus tractus solitarius, NTS)水平相互作用，跨转调节CSR，尚不清楚。本文在麻醉Sprague-Dawley (SD)大鼠孤离的一侧颈动脉窦区，通过窦内逐级加压引发CSR和动脉血压变化，经Logistic五参数曲线拟合，求得窦内压(intracarotid sinus pressure, ISP)–平均动脉压(mean arterial pressure, MAP)关系曲线及其特征参数，观察预先在NTS微量注射各选择性胆碱能受体拮抗剂[M1受体拮抗剂哌仑西平(pirenzepine, PRZ)、M2受体拮抗剂美索曲明(methoctramine, MTR)或N1受体拮抗剂六烃季胺(hexamethonium, HEX)]对侧脑室微量注射(intracerebroventricular injection, i.c.v.)组胺(histamine, HA)所致CSR变化的影响，以及预先在NTS微量注射组胺能H1受体拮抗剂氯苯吡胺(chlorpheniramine, CHL)或H2受体拮抗剂西咪替丁(cimetidine, CIM)对i.c.v.拟胆碱药毒扁豆碱(physostigmine, PHY)所致CSR变化的影响，以期解析中枢两大系统对CSR是否具有跨转调节机制。结果显示：(1)单独NTS内注射所给剂量的各选择性胆碱能受体拮抗剂或组胺能受体拮抗剂对CSR均无明显作用(P > 0.05)，也不引起动脉血压水平明显变动；(2)预先NTS内注射PRZ或MTR可部分翻转i.c.v. HA所致的CSR重调定，表现为ISP–MAP关系曲线在高窦压区明显左下移位(P < 0.05)，ISP–Gain关系曲线在中窦压区显著上移(P < 0.05)，反射参数平均动脉压变动范围和最大增益加大(P < 0.05)，最大增益时的窦内压值与饱和压减少(P < 0.05)，上述效应中PRZ的作用不如MTR的显著(P < 0.05)，但HEX对i.c.v. HA所致的CSR变化无明显作用(P > 0.05)；(3)预先NTS内注射CHL或CIM对i.c.v. PHY所致CSR变化的影响，类似于NTS内注射PRZ或MTR对i.c.v. HA所致CSR变化的作用，且CHL的效应强于CIM (P < 0.05)。上述结果表明：侧脑室注射HA所致的CSR重调定机制可能涉及下丘脑-NTS下行组胺能通路，跨转激活NTS的胆碱能系统，经M1、M2受体尤其是M2受体介导而发挥调节作用；侧脑室注射PHY对CSR的重调定，可能通过下丘脑-NTS下行胆碱能通路，跨转激活NTS的组胺能系统，经H1、H2受体尤其是H1受体介导而生效。

关键词： 颈动脉窦压力感受器反射; 孤束核; 胆碱能受体; 组胺能受体; 侧脑室; 组胺; 毒扁豆碱; Logistic方程; 平均动脉压

分类号：Q463;R331.3;R544

[Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex.] [Article in Chinese]

HU Li-Xun, ZHANG Guo-Xing, ZHANG Yu-Ying, ZHAO Hong-Fen, YU Kang-Ying, WANG Guo-Qing

Department of Physiology, School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China

Abstract

The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M₁ receptor antagonist, i.e., pirenzepine (PRZ), the M₂ receptor antagonist, i.e., methoctramine (MTR) or the N₁ receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H₁ receptor antagonist, i.e., chlorpheniramine (CHL) or the H₂ receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M₁ and M₂ receptors mediation, especially the M₂ receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H₁ and H₂ receptors mediation, especially the H₁ receptors displaying effects.

Key words: carotid sinus baroreceptor reflex; nucleus tractus solitarius; cholinergic receptors; histaminergic receptors; lateral ventricle; histamine; physostigmine; logistic equation; mean arterial pressure

收稿日期：2013-04-18　　录用日期：2013-07-02

通讯作者：王国卿　　E-mail: wangguoqing@suda.edu.cn

引用本文：

胡力旬, 张国兴, 张玉英, 赵红芬, 于康英, 王国卿. 孤束核胆碱能与组胺能系统对颈动脉窦压力感受器反射调节的交互作用[J]. 生理学报 2013; 65 (6): 607-615.

HU Li-Xun, ZHANG Guo-Xing, ZHANG Yu-Ying, ZHAO Hong-Fen, YU Kang-Ying, WANG Guo-Qing. [Involvement of cross interaction between central cholinergic and histaminergic systems in the nucleus tractus solitarius in regulating carotid sinus baroreceptor reflex.] [Article in Chinese]. Acta Physiol Sin 2013; 65 (6): 607-615 (in Chinese with English abstract).