Copyright © 2004, European Society of Cardiology
Urocortin-induced relaxation in the human internal mammary artery
aCardiovascular Research, Starr Academic Center for Cardiac Surgery, Providence Heart and Vascular Institute and Department of Surgery, Oregon Health and Science University, Portland, U.S.A.
bDepartment of Physiology, The Chinese University of Hong Kong, Hong Kong SAR, China
cDepartment of Bioengineering, University of Washington Seattle, U.S.A.
dDepartment of Surgery, The Chinese University of Hong Kong, Hong Kong SAR and Wuhan Heart Institute, The Central Hospital of Wuhan, Wuhan, China
* Corresponding author. Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China. Tel.: +852 26450519; fax: +852 26451762. Email address: gwhe{at}cuhk.edu.hk
Objective: Urocortin, a potent vasodilator, plays physiological or pathophysiological roles in the cardiovascular system. However, little is known about its action in human vascular tissues. The present study was designed to investigate the vascular effect of urocortin on human internal mammary artery (IMA) in vitro and the possible underlying mechanisms.
Methods: Human IMA was obtained from patients undergoing coronary artery bypass grafting. The isolated IMA rings were mounted in organ baths and changes in isometric tension were measured by using Grass force–displacement transducer. Corticortropin-releasing factor-receptors (CRF-R) were also analyzed in the IMA by using RT-PCR analysis.
Results: In 9,11-dideoxy-11
,9-epoxy-methanoprostaglandin F2 (U46619
[GenBank]
)-precontracted endothelium-intact rings, urocortin induced concentration-dependent relaxations with pD2 of 8.69 ± 0.11 and this effect was markedly reduced in endothelium-denuded rings. Relaxations to urocortin in endothelium-intact rings were attenuated to the same extent after treatment with NG-nitro-L-arginine (L-NNA) and 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one (ODQ). Urocortin-induced relaxations were also inhibited by treatment with putative K+ channel blockers, such as tetraethylammonium (TEA+), charybdotoxin (CTX), and iberiotoxin (IBX). In endothelium-denuded rings, treatment with TEA+, CTX, or IBX attenuated relaxation to urocortin as well as sodium nitroprusside (SNP). The bands for CRF-R1, CRF-R2, and CRF-R2β mRNAs were observed in both endothelium-intact and endothelium-denuded human IMA.
Conclusion: Urocortin produced both endothelium-dependent and -independent relaxation in human IMA rings. The endothelium-dependent component primarily involves the release of endothelial nitric oxide (NO) that in turn stimulates Ca2+-activated K+ channels in vascular smooth muscle via cyclic GMP-dependent mechanisms. CRF-R1, CRF-R2, and CRF-R2β mRNAs are present in the human IMA.
KEYWORDS Arteries; K-channels; Signal transduction; Vasoconstriction/dilation; CRF receptor
Time for primary review 21 days
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