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Ann Thorac Surg 2003;75:874-881
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Endothelin receptors in endothelium-denuded human coronary artery bypass grafts and coronary arteries

^a Department of Internal Medicine, Lund University Hospital, Lund, Sweden
^b Department of Cardiothoracic Surgery, Lund University Hospital, Lund, Sweden

Accepted for publication October 3, 2002.

^* Address reprint requests to A. Wackenfors, Division of Experimental Vascular Research, BMC A13, Lund University Hospital, SE-22184 Lund, Sweden.
e-mail: angelica.wackenfors{at}med.lu.se

BACKGROUND: Coronary artery bypass graft (CABG) surgery is hampered by deleterious vasospasm in the vessel wall, especially in vein grafts. Endothelin (ET) is a strong vasoconstrictor that can be observed in increasing concentrations during CABG surgery.

METHODS: Endothelin-induced vasoconstriction was evaluated in isolated, endothelium-denuded vessel segments of the human saphenous vein (SV), left internal mammary artery (LIMA), and coronary arteries. The ET_A and ET_B receptor mRNA levels were quantified by real-time polymerase chain reaction (PCR) analysis.

RESULTS: The ET_A and ET_B receptor mRNA levels were significantly higher in the SV than in the LIMA and the coronary arteries. ET-1 induced a more efficacious contraction in the SV and LIMA as compared with in the coronary arteries. The ET_B receptor agonist, Sarafotoxin 6c (S6c) stimulated constriction of the LIMA and SV, while inactive in the coronary arteries. The concentration-response curve for S6c was biphasic, suggesting activation of ET_A receptors at high concentrations as this response could be inhibited by FR139317 (10 µmol/L), and ET_B at low concentrations as this response could be inhibited by BQ788 (0.1 µmol/L).

CONCLUSIONS: Endothelin-induced vasoconstriction is mediated by ET_A receptors alone in coronary arteries, while a combination of ET_A and ET_B receptors are of importance in SV and LIMA. Expression of contractile ET_B receptors may be a pharmacologic disadvantage that contributes to the vasospasm during CABG surgery. The lower levels of ET_A and ET_B receptor mRNA in the LIMA and coronary arteries as compared with in the SV may provide one explanation for the better long- and short-term patency of LIMA as compared with SV grafts.

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