Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries

Little information is available regarding the vasoactive effects of epoxyei cosatrienoic acids (EETs) in the lung. We demonstrate that 5,6-, 8,9-, 11,1 2-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a conc entration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-E ET is blocked by indomethacin or ibuprofen (10(-5) M), SQ-29548, endothelia l denuding, or submaximal preconstriction with the thromboxane mimetic U-46 619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxy phenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabo lize arachidonate to products that comigrate on reverse-phrase HPLC with au thentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxy genase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E , CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and p eripheral lung microsomes. Constriction of isolated rabbit pulmonary arteri es to EETs is nonregioselective and depends on intact endothelium and cyclo oxygenase, consistent with the formation of a presser prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.