@article {Moreland446, author = {K. Trent Moreland and Jesse D. Procknow and Randy S. Sprague and Jennifer L. Iverson and Andrew J. Lonigro and Alan H. Stephenson}, title = {Cyclooxygenase (COX)-1 and COX-2 Participate in 5,6-Epoxyeicosatrienoic Acid-Induced Contraction of Rabbit Intralobar Pulmonary Arteries}, volume = {321}, number = {2}, pages = {446--454}, year = {2007}, doi = {10.1124/jpet.106.107904}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Epoxyeicosatrienoic acids (EETs) have been reported to contract intralobar pulmonary arteries (PA) of the rabbit in a cyclooxygenase (COX)-dependent manner. In the present study, we observed that COX-1 and COX-2 isoforms were expressed in freshly isolated PA of healthy rabbits. We examined the hypothesis that both COX isoforms participate in 5,6-EET-induced contraction of rabbit intralobar PA. Selective inhibition of COX-1 with 300 nM 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560) prevented 5,6-EET (1 {\texttimes} 10{\textendash}8{\textendash}1 {\texttimes} 10{\textendash}5 M)-induced contractions of isolated intralobar rabbit PA rings in a manner similar to that observed with the nonselective cyclooxygenase inhibitor indomethacin at 10 μM. Selective inhibition of COX-2 with either 100 nM 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonyl) thiophene (DUP-697) or 3 μM N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) shifted the EC50 value of 5,6-EET-induced PA contraction to the right but with considerably lower efficacy than SC-560. In rabbit PA, 5,6-EET-induced contraction was primarily dependent on COX-1 activity. Differential metabolism of 5,6-EET by COX-1 and COX-2 does not explain the primary dependence of PA contraction on COX-1 activity because 5,6-EET was metabolized similarly by both COX isoforms. COX-1 and -2 were expressed primarily in PA endothelium where COX-1 expression was dense and uniform, whereas COX-2 expression was sparse and nonuniform. 5,6-EET-induced PA contraction was endothelium-dependent. These results suggest that 5,6-EET-induced contraction is primarily dependent on COX-1 activity. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/321/2/446}, eprint = {https://jpet.aspetjournals.org/content/321/2/446.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }