蓝斑H_1受体介导应激对颈动脉窦反射的抑制作用

Role of the H_1 Receptors in the Locus Ceruleus in Stress-induced Inhibition of Carotid Sinus Reflex in Rats

目的揭示蓝斑H1受体在应激对颈动脉窦反射(CSR)抑制中的作用。方法应激1周的SD大鼠,麻醉后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曲线拟合,求得ISP-MAP关系曲线及其反射特征参数,观察蓝斑注射选择性H1受体拮抗剂氯苯吡胺(CHL)对应激条件下CSR的影响。结果蓝斑内注射CHL(0.5μg/μl)导致应激大鼠ISP-MAP关系曲线显著下移,反射参数中阈压、饱和压和最大增益时的窦内压值均减小,而MAP变动范围与反射最大增益加大,这些变化均有统计学意义(均P<0.05);蓝斑注射相同剂量的CHL对非应激大鼠的CSR无明显影响(P>0.05);蓝斑内注射CHL不能使应激的CSR水平完全恢复到非应激给药后水平。结论蓝斑H1受体参与应激对CSR的抑制作用;除此之外,应激效应中尚有其他因素的参与。

Objective To explore the effects of H1 receptors in the locus eeruleus （LC） on inhibition of carotid sinus reflex（CSR） induced by the stress. Methods Male Sprague-Dawley rats were divided into two groups at random： the unstressed（n=7） and stressed group （n=8）. The latter was subjected to unavoidable electric foot-shock twice daily for a week, each session of foot-shock lasted 2 hours. The left and right carotid sinus regions were isolated from the systemic circulation in all animals anesthetized with pentobarbital sodium. The intracarotid sinus pressure（ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. We observed the changes in CSR performance resulting from the stress and the effects of microinjection of H1 receptor selective antagonist, ehlorpheniramine （CHL） into LC on the responses of CSR to stress. Results Mieroinjection of CHL （0.5 μg, in 1 μl） significantly shifted the ISP-MAP relationship curve downwards（P〈0.05） and obviously decreased the value of the reflex parameters such as the threshold pressure, saturation pressure and ISP at the maximum gain （P〈0.05）, but remarkably increased the MAP range and the maximum gain （P〈0.05） in the stressed rats. Microinjection with the same dose of CHL into the LC in the unstressed rats did not change CSR performance significantly （P〉0.05）. The changes in the stressed CSR performance resulted from the microinjection of CHL into the LC did not recover the levels of unstressed CSR after injection. Conclusion H1 receptors in the LC is involved in the stress-induced functional inhibition of CSR, and at the same time, the effects of stress on CSR also have other mechanism.