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

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 micromol/L), and ET(B) at low concentrations as this response could be inhibited by BQ788 (0.1 micromol/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.