外周α_1受体作用减轻脑室注射组胺对颈动脉窦反射的抑制

Peripheral α1 Receptors Attenuate Inhibition of Carotid Sinus Baroreflex Induced by Intracerebroventricular Injection of Histamine in Anesthetized Rats

目的 研究外周α1受体是否参与调制中枢外源性组胺(HA)对颈动脉窦反射(CBR)的抑制。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,根据所得ISP-MAP关系曲线及其特征参数,观察脑室注射(icv)HA及预先外周静脉注射(iv)选择性α1受体拮抗剂酚苄明(PBZ)对CBR的影响。结果 icv HA(60 μmol／L,5 μl)导致ISP-MAP关系曲线明显上移,反射参数中阈压、饱和压和最大增益时的窦内压值增大(P<0.05),MAP反射变动范围及反射最大增益减小(P<0.05);预先iv PBZ(3μmol／L,15μl／100 g体重),明显进一步加强HA的上述效应;单独iv相同剂量的PBZ对CBR无明显影响(P>0.05)。结论 脑室给HA使CBR产生快速重调定,反射敏感性下降;外周α1受体作用可减弱icvHA对CBR的抑制性重调定。

Objective To determine the role of peripheral α1 receptors in inhibition of carotid sinus baroreflex (CBR) induced by intracerebroventricular (icv) injection of histamine (HA). Methods The left and right carotid sinus regions were isolated from the systemic circulation in 28 male Sprague-Dawley rats 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. The changes in CBR performance induced by icv HA and the effects of pretreatment with α1 receptor selective antagonist, phenoxybenzamine (PBZ) injected into the peripheral vein, on the responses of CBR to HA were observed. Results Icv HA (60 μmol / L in 5 μl) significantly shifted the ISP-MAP relationship curve upwards and obviously decreased the value of the reflex parameters such as MAP changing range and maximum gain (P < 0.05), but increased the threshold pressure, saturation pressure and ISP at maximum gain (P<0.05). The peripheral pretreatment of PBZ (3μmol / L, in 15 μl / 100 g weight) could obviously intensify the above-mentioned changes of CBR induced by HA. Peripheral intravenous injection with the same dose of PBZ alone did not change CBR performance significantly ( P >0.05). Conclusion HA intracerebroventricular administration could result in the rapid resetting ofCBR, the decrease of reflex sensitivity and the responses of CBR to HA might be attenuated by peripheral α1 receptor activity.