Noradrenaline-induced contraction mediated by endothelial COX-1 metabolites in the rat coronary artery.

Noradrenaline-induced contraction of the rat coronary arteries was significantly augmented by the presence of NG-nitro-L-arginine methyl ester (L-NAME) and arachidonic acid. The experiments in the study presented here were undertaken to characterize pharmacologically the augmented noradrenaline-induced contraction in ring preparations of rat coronary arteries. The contraction was stopped by a chemical remover of endothelium (saponin). Oxygen radical scavengers, superoxide dismutase and catalase, significantly attenuated the contraction. Cyclooxygenase-1 inhibitors (flurbiprofen, 10(-7) M) attenuated the noradrenaline-induced contraction and cyclooxygenase-2 (nimesulide, 10(-7) M) slightly attenuated the contraction. A thromboxane A2 (TXA2) synthetase inhibitor (OKY-046) and a TXA2 receptor antagonist (S-1452) did not affect the contraction. Based on these results, it was suggested that the contraction induced by noradrenaline in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium-dependent, and that it involves reactive oxygen species and endothelial cyclooxygenase-1 metabolites of arachidonic acid.