外周α_1、α_2受体作用减弱脑室注射组胺对颈动脉窦反射的抑制

Peripheral α_1 and α_2-adrenoceptors involved in attenuating the intracere broventricular histamine-induced carotid sinus baroreceptor reflex inhibition in rats

目的 探讨外周α1 和α2 肾上腺素受体 (α1 AR,α2AR)在脑室注射(icv)组胺 (HA)对颈动脉窦压力感受性反射(CSR)重调定中的作用。方法 孤离麻醉SD大鼠的双侧颈动脉窦区,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,求得ISP MAP关系曲线及其特征参数,观察icvHA以及预先在外周静脉注射(iv)α1 或α2 AR拮抗剂对CSR的影响。结果 icvHA( 60μmol·L-1, 5μl)导致ISP MAP关系曲线后半程明显上移(P<0 05),ISP和增益关系曲线中部明显下移 (P<0 05 ),反射参数MAP反射变动范围及反射最大增益减小 (P<0 05),而阈压与饱和压增大(P<0 05);预先外周iv选择性的α1 AR拮抗剂酚苄明 (PBZ, 2 5μmol·L-1, 0 15μl·g-1 )或α2 AR拮抗剂育亨宾(YOH, 5μmol·L-1, 0 15μl·g-1 ),均能明显加强HA的上述效应,YOH的这种加强作用不如PBZ的显著 (P<0 05 );单独外周iv相同剂量的PBZ或YOH对CSR无影响 (P>0 05 )。结论 脑室给HA使CSR产生快速重调定,反射敏感性下降;外周α1、α2 AR作用可减弱icvHA对CSR的重调定;外周α1 AR在调制这种抑制性重调定的过程中可能发挥重要作用。

Aim To determine the roles of peripheral α 1 and α 2 -adrenoceptors (α 1-AR,α 2-AR) in inhibition of carotid sinus barore ceptor reflex(CSR) induced by intracerebroventricular injection (icv) of histami ne (HA).Methods The left and right carotid sinus regions were i solated from the systemic circulation in 22 male Sprague-Dawley rats anesthetiz ed with pentobarbital sodium.The intracarotid sinus pressure (ISP) was altered in a stepwise ma nner in vivo.ISP-mean arterial pressure (MAP) relationship curve and its ch aracteristic parameters were constructed by fitting to the logistic function wit h five parameters.The changes in CSR performance induced by icv HA and the effec ts of pretreatment with α 1-AR or α 2-AR selective antagonist into the per ipheral vein on the responses of CSR to HA were examined.Results icv microinjection of HA (60 μmol·L -1 in 5 μl) significantly shifted the ISP-MAP relationship curve upwards (P<0.05) and moved the middle part of ISP-Gain relationship curve downwards (P<0.05), and reduced the MAP range and maximum gain(P<0.05) but increased the thresh old pressure and saturation pressure(P<0.05).The pretreatment with phenoxybenzamine(PBZ,a selective antagonist of α 1-AR,2.5 μmol·L -1,0.15 μl·g -1) or yohimbine (YOH,a selective antagonist of α 2-AR,5 μmol·L -1,0.15 μl·g -1)into the peripheral vein could obviously intensify the above-mentioned changes in CSR performance induced by HA, but the intensive effect of YOH was less remarkable than that of PBZ (P<0.05).Without icv HA, injection of PBZ or YOH into the peripheral vein with the respectively corresponding dose and volume, had no effect on the CSR performance (P>0.05).Conclusion The intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the functions of both the peripheral α 1-AR and α 2-AR may attenuate CSR resetting induced by icv microinjection of HA. Furthermore,the peripheral α 1-AR might play an important role in mediating the responses of CSR to central HA.