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- Title
Roles of cyclic AMP and Ca<sup>2+</sup>-activated K<sup>+</sup> channels in endothelium-independent relaxation by urocortin in the rat coronary artery
- Authors
Huang, Yu; Chan, Franky Leung; Lau, Chi-Wai; Tsang, Suk-Ying; Chen, Zhen-Yu; He, Guo-Wei; Yao, Xiaoqiang
- Abstract
<B>Objective:</B> 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. <B>Methods:</B> Changes in vessel tension were measured by using a force transducer built in a Multi Myograph System. <B>Results:</B> In 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F2α (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+. <B>Conclusion:</B> 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.
- Subjects
ARTERIES; CELLULAR signal transduction
- Publication
Cardiovascular Research, 2003, Vol 57, Issue 3, p824
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/S0008-6363(02)00773-3