NaHS relaxes rat cerebral artery in vitro via inhibition of l-type voltage-sensitive Ca 2+ channel

Xiao Yu Tian, Wing Tak Wong, Nazish Sayed, Jialie Luo, Suk Ying Tsang, Zhao Xiang Bian, Ye Lu, Wai San Cheang, Xiaoqiang Yao, Zhen Yu Chen, Yu Huang

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalPharmacological Research
Volume65
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • Ca channel
  • Hydrogen sulfide
  • Rat cerebral artery
  • Vasodilatation
  • l-cysteine

ASJC Scopus subject areas

  • Pharmacology

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