NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage-sensitive Ca2+ channel

• Published in: Pharmacological research Vol. 65; no. 2; pp. 239 - 246
• Main Authors: Tian, Xiao Yu, Wong, Wing Tak, Sayed, Nazish, Luo, Jialie, Tsang, Suk Ying, Bian, Zhao Xiang, Lu, Ye, Cheang, Wai San, Yao, Xiaoqiang, Chen, Zhen Yu, Huang, Yu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-2012
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Ca2+ channel; Calcium - metabolism; Calcium Channels, L-Type - metabolism; Cerebral Arteries - drug effects; Cerebral Arteries - metabolism; Cerebral Arteries - physiology; Cystathionine gamma-Lyase - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiology; Hydrogen sulfide; Hydrogen Sulfide - metabolism; l-cysteine; Male; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - physiology; Rat cerebral artery; Rats; Rats, Sprague-Dawley; Sulfides - metabolism; Sulfides - pharmacology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilatation; Vasodilation - drug effects; Vasodilation - physiology; Hydrogen sulfide; Vasodilatation; l-cysteine; Rat cerebral artery; Ca2+ channel
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2011.11.006

H2S, a gaseous signalling molecule, relaxes blood vessels partly through activation of ATP-sensitive K+ channels. It is however unclear whether H2S or its donors could affect other ion transporting proteins. The present study examined the hypothesis that NaHS, a H2S donor inhibits voltage-sensitive Ca2+ channels and thus relaxes vascular smooth muscle cells (VSMC) in the cerebral arteries. NaHS dilated cerebral arteries from Sprague–Dawley rats with the same potency against pre-contraction by 5-HT and 60mmol/L KCl, which were unaffected by several K+ channel blockers, NG-nitro-l-arginine methyl ester or indomethacin, as assessed in wire myograph under an isometric condition. Likewise, NaHS also dilated cerebral arteries against myogenic constriction in pressurized myograph under an isobaric condition. NaHS concentration-dependently inhibited CaCl2-induced contraction in Ca2+-free, 60mM K+-containing Krebs solution. Patch clamp recordings showed that NaHS reduced the amplitude of l-type Ca2+ currents in single myocytes isolated enzymatically from the cerebral artery. Calcium fluorescent imaging using fluo-4 showed a reduced [Ca2+]i in 60mmol/L KCl-stimulated rat cerebral arteries in response to NaHS. H2S precursor l-cysteine-induced relaxation in cerebral arteries was inhibited by cystathionine γ–lyase (CSE) inhibitor dl-propargylglycine. CSE was expressed in cerebral arteries. In summary, NaHS dilates rat cerebral arteries by reducing l-type Ca2+ currents and suppressing [Ca2+]i of arterial myocyte, indicating that NaHS relaxes cerebral arteries primarily through inhibiting Ca2+ influx via Ca2+ channels