© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Roles of cyclic AMP and Ca2+-activated K+ channels in endothelium-independent relaxation by urocortin in the rat coronary artery
aDepartment of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China
bDepartment of Anatomy, Chinese University of Hong Kong, Hong Kong, China
cDepartment of Biochemistry, Chinese University of Hong Kong, Hong Kong, China
dDepartment of Surgery, Chinese University of Hong Kong, Hong Kong, China
* Corresponding author. Tel.: +852-26-096-787; fax: +852-26-035-022. yu-huang{at}cuhk.edu.hk
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-11
,9-epoxy-methanoprostaglandin F2 (U46619
[GenBank]
)-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
[GenBank]
-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.
KEYWORDS Arteries; K-channel; Signal transduction; Vasoconstriction/dilation
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