Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Franky Leung Chan
  • Chi-Wai Lau
  • Suk-Ying Tsang
  • Zhen-Yu Chen
  • Guo-Wei He
  • Xiaoqiang Yao

Detail(s)

Original languageEnglish
Pages (from-to)824-833
Journal / PublicationCardiovascular Research
Volume57
Issue number3
Publication statusPublished - 1 Mar 2003
Externally publishedYes

Abstract

Objective: Urocortin possesses cardioprotective properties against the damaging effects of ischemia/reperfusion injury. Our previous study demonstrated that urocortin can induce both endothelium-dependent and -independent coronary relaxation. However, the mechanisms thereby urocortin triggers endothelium-independent relaxation have not been investigated. The present study aimed to examine the role of cyclic AMP and Ca2+-activated K+ channels in the relaxant response to urocortin in the isolated endothelium-denuded rat left anterior descending coronary arteries. Methods: Changes in vessel tension were measured by using a force transducer built in a Multi Myograph System. Results: In 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F (U46619)-contracted rings, urocortin-induced relaxation (pD2: 8.40±0.04) was significantly reduced by cyclic AMP-dependent protein kinase (PKA) inhibitors, Rp-cAMPS triethylamine (Rp-cAMPS) and KT 5720. Treatment with the large-conductance Ca2+-activated K+ channel blockers, iberiotoxin or tetraethylammonium ions (TEA+) attenuated urocortin-induced relaxation; this effect was abolished in the presence of 200 nmol/l KT 5720. In contrast, apamin (small-conductance Ca2+-activated K+ channel blocker), glibenclamide (ATP-sensitive K+ channel blocker), or BaCl2 (inwardly rectifier K+ channel blocker) had no effect. Urocortin-induced relaxation was reduced in rings contracted with increasing concentrations of extracellular K+ (35 and 50 mmol/l). Treatment with TEA+ or Rp-cAMPS inhibited the relaxant effect of urocortin in 35 mmol/l K+-contracted rings. Combined treatment with TEA+ and Rp-cAMPS had no additional effect. Similarly, forskolin produced significantly less relaxant response in 50 mmol/l K+-contracted than U46619-contracted rings. Forskolin-induced relaxation was attenuated by pretreatment with 3 mmol/l TEA+. Conclusion: Urocortin relaxed the rat coronary artery in substantial part via activation of the vascular Ca2+-activated K+ channels and this effect appears to be primarily mediated through PKA-dependent intracellular mechanisms. © 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Research Area(s)

  • Arteries, K-channel, Signal transduction, Vasoconstriction/dilation

Bibliographic Note

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Citation Format(s)

Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery. / Huang, Yu; Chan, Franky Leung; Lau, Chi-Wai et al.
In: Cardiovascular Research, Vol. 57, No. 3, 01.03.2003, p. 824-833.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review