Endothelin-1 releases endothelium derived endoperoxides and thromboxane A(2) in porcine coronary arteries with regenerated endothelium

AIM: To determine the role of endothelium-derived contracting factor (EDCF) in the response to endothelin-l in arteries with regenerated endothelium. METHODS: Rings of porcine coronary arteries, with and without endothelium o f previously deendothelialized left anterior descending coronary arteries a nd native left circumflex coronary arteries, were suspended in conventional organ chambers for the measurement of isometric force. RESULTS: In quiesce nt rings of the previously deendothelialized left anterior descending coron ary artery treated with the NO-synthase inhibitor nitro-L-arginine, endothe lin-l caused contractions which were larger in rings with than that in thos e without endothelium. Under the same experimental conditions, in the left- circumflex coronary artery, the contractions to endothelin-1 were augmented markedly by the removal of the endothelium. In rings with endothelium of t he previously deendothelialized left anterior descending coronary artery, i ndometacin (inhibitor of cyclooxygenase) and ridogrel (thromboxane A(2) rec eptor antagonist and inhibitor of thromboxane synthase) inhibited contracti ons to endothelin-1. The endothelium-dependent component of the response to lower concentrations of endothelin-1 was inhibited by indometacin and rido grel, but not by dazoxiben. In rings without endothelium of both previously deendothelialized left anterior descending and native left circumflex coro nary arteries, indometacin and ridogrel did not affect the contractions to endothelin-1. CONCLUSION: These findings suggest that in regenerated endoth elium, high concentrations of endothelin-1 stimulate the release of thrombo xane A(2) Endoperoxides generated by activation of endothelial cyclooxygena se may be the endothelium-derived contracting factor(s) released in regener ated endothelium by lower concentrations of the peptide.