GABA 受体、钾通道和 L 型钙通道与 HS 增强自发性高血压大鼠压力感受器反射的易化效应有关。

GABA receptor, K channel and L-type Ca channel is associated with facilitation effect of HS on the baroreceptor reflex in spontaneous hypertensive rats.

机构信息

Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China; Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China.

Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, China.

出版信息

Pharmacol Rep. 2019 Oct;71(5):968-975. doi: 10.1016/j.pharep.2019.05.009. Epub 2019 May 15.

DOI:10.1016/j.pharep.2019.05.009

PMID:31470293

Abstract

BACKGROUND

We aimed to investigate whether the facilitating effect of HS on the baroreceptor reflex is associated with the GABA receptor, K channel and L-type Ca channel pathway.

METHODS

Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used to investigate the facilitating effect of HS on the baroreceptor reflex by perfusing the isolated carotid sinus. The mechanism by which HS facilitated the baroreceptor reflex was determined by using Bay K8644 (an agonist of calcium channels), glibenclamide (Gli, a K channel blocker), and picrotoxin (PIC, a blocker of γ-aminobutyric acid [GABA] receptor).

RESULTS

As compared with WKY rats, SHRs showed impaired baroreceptor reflex sensitivity, as demonstrated by a right and upward shift of the functional curve for the intrasinus pressure-arterial blood pressure relation. HS perfusion (25, 50, or 100 μmol/L) dose-dependently ameliorated the impaired sensitivity of the baroreceptor reflex. Bay K8644 (500 nmol/L), Gli (20 μmol/L) and PIC (50 μmol/L) all prevented HS ameliorating the impaired baroreceptor reflex.

CONCLUSIONS

HS facilitating the baroreceptor reflex might be associated with activating the GABA receptor, opening the K channel, and closing the L-type Ca channel. These areas should provide new targets for preventing and treating hypertension.

摘要

背景

本研究旨在探讨 HS 对压力感受器反射的易化作用是否与 GABA 受体、K 通道和 L 型 Ca 通道途径有关。

方法

采用分离颈动脉窦灌流的方法，观察 HS 对自发性高血压大鼠（SHR）和 Wistar Kyoto（WKY）大鼠压力感受器反射的易化作用，并用 Bay K8644（钙通道激动剂）、格列本脲（Gli，K 通道阻断剂）和荷包牡丹碱（PIC，GABA 受体阻断剂）观察 HS 易化压力感受器反射的机制。

结果

与 WKY 大鼠相比，SHR 大鼠的压力感受器反射敏感性受损，表现为窦内压-动脉血压关系的功能曲线向右上方移位。HS 灌流（25、50 或 100μmol/L）剂量依赖性地改善了压力感受器反射的敏感性受损。Bay K8644（500nmol/L）、Gli（20μmol/L）和 PIC（50μmol/L）均阻止 HS 改善压力感受器反射的敏感性受损。