Abstract:
AIMS:Endothelium-dependent vasorelaxation is mediated by endothelium-derived relaxing factor and endothelium-derived hyperpolarizing factor (EDHF). However, the molecular entity of EDHF remains unclear. The present study examined whether hydrogen sulfide (H₂S) acts as EDHF and how H₂S mediates EDHF pathways from endothelial origination to downstream target of smooth muscle cells (SMCs). RESULTS:We found that knocking-out the expression of cystathionine γ-lyase (CSE) in mice (CSE-knockout [KO]) elevated resting-membrane-potential of SMCs and eliminated methacholine-induced endothelium-dependent relaxation of mesenteric arteries, but not that of aorta. Methacholine, a cholinergic-muscarinic agonist, hyperpolarized SMC in endothelium-intact mesenteric arteries from wide-type mice. This effect was inhibited by muscarinic antagonist (atropine) or the co-application of charybdotoxin and apamin, which blocked intermediate- and small-conductance KCa (IKCa and SKCa) channels, or abolished in CSE-KO mice. Supplementation of exogenous H₂S hyperpolarized vascular SMCs and endothelial cells from wide-type and CSE-KO mice. Both methacholine and H₂S induced greater SMC hyperpolarization of female wide-type mesenteric arteries than that of male ones. H2S-induced hyperpolarization is blocked by -SH oxidants and -SSH inhibitor. The expression of SK2.3 but not IK3.1 channel in vascular tissues was increased by H₂S and decreased by CSE inhibitor or CSE gene KO. INNOVATION AND CONCLUSIONS:Taken together, H₂S is an EDHF. The identification of H2S as an EDHF will not only solve one of the long-lasting perplexing puzzles for the mechanisms underlying endothelium-dependent vasorelaxation, but also shed light on potential therapeutic effects of H₂S on pathological abnormalities in peripheral resistance arteries.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Tang G,Yang G,Jiang B,Ju Y,Wu L,Wang Rdoi
10.1089/ars.2012.4805subject
Has Abstractpub_date
2013-11-10 00:00:00pages
1634-46issue
14eissn
1523-0864issn
1557-7716journal_volume
19pub_type
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