School of Chinese Medicine
NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage-sensitive Ca2+ channel
H 2S, a gaseous signalling molecule, relaxes blood vessels partly through activation of ATP-sensitive K + channels. It is however unclear whether H 2S or its donors could affect other ion transporting proteins. The present study examined the hypothesis that NaHS, a H 2S donor inhibits voltage-sensitive Ca 2+ 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 60 mmol/L KCl, which were unaffected by several K + channel blockers, N G-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 CaCl 2-induced contraction in Ca 2+-free, 60 mM K +-containing Krebs solution. Patch clamp recordings showed that NaHS reduced the amplitude of l-type Ca 2+ currents in single myocytes isolated enzymatically from the cerebral artery. Calcium fluorescent imaging using fluo-4 showed a reduced [Ca 2+] i in 60 mmol/L KCl-stimulated rat cerebral arteries in response to NaHS. H 2S 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 Ca 2+ currents and suppressing [Ca 2+] i of arterial myocyte, indicating that NaHS relaxes cerebral arteries primarily through inhibiting Ca 2+ influx via Ca 2+ channels © 2011 Elsevier Ltd. All rights reserved.
Ca 2+ channel, Hydrogen sulfide, l-cysteine, Rat cerebral artery, Vasodilatation
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Tian, X., Wong, W., Sayed, N., Luo, J., Tsang, S., Bian, Z., Lu, Y., Cheang, W., Yao, X., Chen, Z., & Huang, Y. (2012). NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage-sensitive Ca2+ channel. Pharmacological Research, 65 (2), 239-246. https://doi.org/10.1016/j.phrs.2011.11.006