Sj. Park et al., Endothelin-1 releases endothelium derived endoperoxides and thromboxane A(2) in porcine coronary arteries with regenerated endothelium, ACT PHAR SI, 20(10), 1999, pp. 872-878
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.