Acetylcholine- and Sodium Hydrosulfide–Induced Endothelium-Dependent Relaxation and Hyperpolarization in Cerebral Vessels of Global Cerebral Ischemia–Reperfusion Rat

Journal of Pharmacological Sciences

Zhi-Wu Chen²  Jun Han²  Guo-Wei He¹ 

[1] TEDA International Cardiovascular Hospital, Medical College, Nankai University, China;Department of Pharmacology, Anhui Medical University, China

关键词: endothelium;    nitric oxide;    endothelium-derived hyperpolarizing factor (EDHF);    hydrogen sulphide;    cerebral artery;   

DOI  :  10.1254/jphs.12277FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(42)Cited-By(10)We investigated the effects of endothelium-derived hyperpolarizing factor (EDHF) and the role of hydrogen sulphide (H2S) in the cerebral vasorelaxation induced by acetylcholine (ACh) in global cerebral ischemia–reperfusion (CIR) rats. CIR was induced by occlusion of bilateral carotid and vertebral arteries. Isolated arterial segments from the cerebral basilar (CBA) and middle artery (MCA) of CIR rats were studied in a pressurized chamber. Transmembrane potential was recorded using glass microelectrodes to evaluate hyperpolarization. In the CIR CBAs and MCAs preconstricted by 30 mM KCl, ACh induced concentration-dependent vasorelaxation and hyperpolarization that were partially attenuated by NG-nitro-l-arginine methyl ester (l-NAME, 30 μM) and l-NAME plus indomethacin (10 μM). The residual responses were abolished by the H2S inhibitor dl-propargylglycine (PPG, 100 μM). The H2S donor NaHS and l-Cys, the substrate of endogenous H2S synthase, elicited similar responses to ACh and was inhibited by tetraethylamonine (1 mM) or PPG. ACh induces EDHF-mediated vasorelaxation and hyperpolarization in rat cerebral arteries. These responses are up-regulated by ischemia–reperfusion while NO-mediated responses are down-regulated. Further, the ACh-induced, EDHF-mediated relaxation, and hyperpolarization and the inhibition of these responses are similar to the H2S-induced responses, suggesting that H2S is a possible candidate for EDHF in rat cerebral vessels.

【 授权许可】

Unknown