GABA(A) receptor, K-ATP channel and L-type Ca2 channel is associated with facilitation effect of H2S on the baroreceptor reflex in spontaneous hypertensive rats

GABA(A) receptor, K-ATP channel and L-type Ca2 channel is associated with facilitation effect of H2S on the baroreceptor reflex in spontaneous hypertensive rats
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GABA(A)受体、K-ATP通道和L-型Ca2+通道与H2S对自发性高血压大鼠压力感受器反射的促进作用相关

DOI:
10.1016/j.pharep.2019.05.009
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发表时间:
2019
影响因子:
4.4
通讯作者:
Wu Yuming
Wu Yuming
中科院分区:
医学3区
文献类型:
--
作者:
Teng Xu;Li Hui;Xue Hongmei;Jin Sheng;Xiao Lin;Guo Qi;Wu Yuming

文献摘要

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本研究旨在探讨H2S对压力受体反射的促进作用是否与gaba受体、KATPchannel和l型Ca2+通道通路有关。方法采用自发性高血压大鼠(SHRs)和Wistar Kyoto大鼠(WKY),观察H2S对离体颈动脉窦内压力感受器反射的促进作用。通过使用Bay K8644(钙通道激动剂)、glibenclamide (KATPchannel阻滞剂)和picrotoxin (γ-氨基丁酸[GABAJA受体阻滞剂)来确定H2S促进压力受体反射的机制。结果与WKY大鼠相比,SHRs的压力感受器反射敏感性受损,表现为脑内压-动脉压关系功能曲线向右上移。H2S灌注(25、50或100 μmol/L)以剂量依赖性改善压力感受反射受损的敏感性。Bay K8644 (500nmol/L)、Gli (20 μmol/L)和PIC (50μmol/L)均能抑制H2S对压力感受反射损伤的改善。结论sh2s促进压力受体反射可能与激活gaba受体、打开KATPchannel、关闭l型Ca2+channel有关。这些领域为高血压防治提供了新的靶点。
BackgroundWe aimed to investigate whether the facilitating effect of H2S on the baroreceptor reflex is associated with the GABAAreceptor, KATPchannel and L-type Ca2+channel pathway.MethodsSpontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were used to investigate the facilitating effect of H2S on the baroreceptor reflex by perfusing the isolated carotid sinus. The mechanism by which H2S facilitated the baroreceptor reflex was determined by using Bay K8644 (an agonist of calcium channels), glibenclamide (Gli, a KATPchannel blocker), and picrotoxin (PIC, a blocker of γ-aminobutyric acid [GABAJA receptor).ResultsAs 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. H2S perfusion (25, 50, or 100 μmol/L) dose-dependently ameliorated the impaired sensitivity of the baroreceptor reflex. Bay K8644 (500nmol/L), Gli (20 μmol/L) and PIC (50μmol/L) all prevented H2S ameliorating the impaired baroreceptor reflex.ConclusionsH2S facilitating the baroreceptor reflex might be associated with activating the GABAAreceptor, opening the KATPchannel, and closing the L-type Ca2+channel. These areas should provide new targets for preventing and treating hypertension.