Involvement of endothelial cyclo-oxygenase metabolites in noradrenaline-induced contraction of rat coronary artery.
1. Noradrenaline (NA; 0.3 micromol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 100 micromol/L) and arachidonic acid (1 micromol/L; P < 0.05). 2. The present experiments attempted to elucidate the endothelium dependency of the contraction and to pharmacologically characterize the factors involved in the contraction induced by NA (0.3 micromol/L) in the presence of L-NAME and arachidonic acid in ring preparations of the rat coronary artery. 3. The NA (0.3 micromol/L)-induced contraction was attenuated by a chemical remover of the endothelium (saponin at concentrations of 0.1 and 0.4 mg/mL) in a concentration-dependent manner (P < 0.05). 4. The cyclo-oxygenase (COX)-1 inhibitor flurbiprofen (0.01-1 micromol/L) and the COX-2 inhibitor nimesulide (0.01-1 micromol/L) attenuated the NA-induced contraction in a concentration-dependent manner and the inhibitory effect of flurbiprofen was significantly more potent than that of nimesulide (P < 0.05). The 5-lipoxigenase inhibitor ZM-230487 (1 micromol/L) did not affect the NA-induced contraction. 5. The thromboxane A2 (TXA2) synthetase inhibitor OKY-046 (30 micromol/L) and the TXA2 antagonist S-1452 (0.1-10 micromol/L) did not attenuate the NA-induced contraction. 6. These results indicate that the contraction induced by NA in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.
Wang
Aimin
A
Pharmacology Division, RI Center, Kyoto University, Kyoto, Japan.
Nishihashi
Tsuyoshi
T
Trandafir
Cristina C
CC
Murakami
Shizuka
S
Ji
Xu
X
Shimizu
Yoshiharu
Y
Kurahashi
Kazuyoshi
K
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013928:Thromboxane A2; D011451:Prostaglandin-Endoperoxide Synthases; D009638:Norepinephrine