Endoperoxides and Thromboxane A2 in Porcine Coronary Arteries with Regenerated Endothelium

ABSTRACT

BACKGROUND: Endothelin-1 is a potent vasoconstrictor substance that causes slow and longlasting contractions of isolated blood vessels. In the aorta of the spontaneously hypertensive rat, endothelin-1 stimulates the release of a cyclooxygenase-dependent, endothelium-derived contracting factor(EDCF), presumably thromboxane A2. There have not been any studies about the response of porcine coronary arteries with regenerated endothelium to endothelin-1. METHODS: The present study was designed to determine the role of EDCF in the response to endothelin-1 in arteries with regenerated endothelium. Rings of porcine coronary arteries, with and without endothelium of previously deendothelialized left anterior descending coronary artery and native left circumflex coronary arteries, were suspended in conventional organ chambers for the measurement of isometric force. RESULTS: In quiescent rings of the previously deendothelialized left anterior descending coronary artery treatd with the nitric oxide synthase inhibitor nitro-Larginine, endothelin-1 caused contractions which were larger in the rings with edothelium than in those without endothelium. Under the same experimental conditions, in the left circumflex coronary artery, the contractions to edothelin-1 were significantly greater by the removal of the endothelium. In rings with endothelium of the previously deendothelialized left anterior descending coronary artery, indomethactin(inhibitor of cyclooxygenase) and ridogrel(thromboxane A2 receptor antagonist, and inhibitor of thromboxane synthase) shifted the concentration-response curve to endothelin-1 to the right and to a comparable extent. Dazoxiben(inhibitor of thromboxane syndthase) and BQ-123(selective antagonist of endothelin-A receptor subtype) inhibited, to the same extent as indomethacin and ridogrel, the response to higher concentrations of endothelin-1. The endothelium-dependent component of the response to lower concentrations of endothelin-1 was inhibited by indomethacin and ridogrel, but not by dazoxiben and BQ-123. In rings without endothelium of both previously deendothelialized left anterior descending and native left circumflex coronary arteries, indomethacin and ridogrel did not affect the contractions to endothelin-1. CONCLUSION: These findings suggest that in regenerated endothelium, high concentrations of endothelin-1 stimulate the release of thromboxane A2 through activation of edothelin-A receptors. Endoperoxides generated by activation of endothelial cyclooxygenase may be the endothelium-derived contracting factor(s) released in regenerated endothelium by lower concentrations of the peptide.