Nicotine-induced contraction in the rat coronary artery: Possible involvement of the endothelium, reactive oxygen species and COX-1 metabolites

Nicotine caused a contraction of the rat coronary artery in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME) and arachidonic acid, and d id not in the absence of these agents. The present experiments were underta ken to pharmacologically characterize the nicotine-induced contraction in r ing preparations of the rat coronary artery. The contraction was abolished by chemical removal of endothelium saponin. Oxygen radical scavengers, supe roxide dismutase and catalase, significantly attenuated the contraction. Cy clooxygenase-1 (COX-1) inhibitors (flurbiprofen, ketoprofen and ketrolack) attenuated the nicotine-induced contraction in a concentration-dependent ma nner, and cyclooxygenase-2 (COX-2) inhibitors at high concentrations (nimes ulide and NS-389) slightly attenuated the contraction. A TXA2 synthetase in hibitor (OKY-046) attenuated the contraction to a small extent only at high concentrations. A TXA2 receptor antagonist (S-1452) attenuated the contrac tion in a concentration-dependent manner. A nicotinic receptor antagonist ( hexamethonium) attenuated the contraction in part and an a-adrenoceptor ant agonist (prazosin) nearly abolished the contraction. From these results, it was suggested that the contraction induced by nicotine in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium depen dent, and involves reactive oxygen species and endothelial COX-1 metabolite s of arachidonic acid. Part of the contraction is probably due to release o f norepinephrine.