八肽胆囊收缩素对大鼠颈动脉窦压力感受器反射的抑制作用(英文)

Cholecystokinin octapeptide inhibits carotid sinus baroreflex in anesthetized rats

在36只隔离灌流颈动脉窦区的麻醉大鼠上,观察了八肽胆囊收缩素(cholecystokinin octapeptide,CCK-8)对颈动脉窦压力感受器反射的影响。其结果如下:(1)以CCK-8(0.1、0.5、1.0 μmol/L)隔离灌流颈动脉窦区时,压力感受器机能曲线向右上方移位,曲线最大斜率(peak slope,PS)减小,反射性血压下降幅度(reflex decrease,RD)减少,阈压(thresholdpressure,TP)和饱和压(saturation pressure,SP)均增高。其中RD、PS和TP呈明显的剂量依赖性;(2)用CCK-8的非特异性受体拮抗剂丙谷胺(100μmol/L)预处理后,能明显减弱CCK-8(0.5μmol/L)对压力感受器反射的抑制;(3)预先灌流一氧化氮合酶(nitric oxide synthase.NOS)阻断剂(L-NAME,100 μmol/L),不能阻断CCK-8(0.5 μmol/L)对压力感受器反射的影响:(4)用Ca2+通道激动剂Bay K 8644(500 nmol/L)预处理后,也能明显减弱CCK-8(0.5 μmol/L)对压力感受器反射的抑制作用。以上结果提示,CCK-8是通过作用于颈动脉窦压力感受器神经元末梢上的受体而起到抑制作用的,其机制可能为抑制了牵张敏感性通道,致使Ca2+离子内流减少,而与内皮细胞释放NO无关。

The purpose of this study was to determine the effect of cholecystokinin octapeptide (CCK-8) on carotid sinus baroreflex in 36 anesthetized male rats by isolated carotid sinus perfusion in vivo. The results obtained are as follows. (1) By perfusion with CCK-8 (0.1, 0.5, 1.0 μmol/L), the functional curve of baroreflex was shifted to the right and upward, with a decrease in peak slope (PS) (P<0.001) and a reflex decrease (RD) in mean arterial pressure, while the threshold pressure (TP) and saturation pressure (SP) were significantly increased. Among the functional parameters of carotid sinus baroreflex, the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with proglumide (100 μmol/L), a nonselective CCK receptor antagonist, the inhibitory effect of CCK-8 (0.5 μmol/L) on the baroreflex was significantly attenuated. (3) Pretreatment with L-NAME (100 μmol/L), an inhibitor of nitric oxide (NO) synthase, did not affect the inhibitory action of CCK-8 (0.5 μmol/L). (4) Preperfusion with Bay K 8644 (500 nmol/L), an agonist of calcium channel, could attenuate the effect of CCK-8 (0.5 μmol/L). It is suggested that the inhibitory action of CCK-8 on the baroreflex may be mediated by the activation of its receptors in the carotid sinus baroreceptor, leading to an inhibition of stretch-sensitive channels and a decrease in Ca2+ influx. However, NO released from the endothelium seems not to be involved in the mechanism of this effect.