Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries

• Published in: American journal of physiology. Lung cellular and molecular physiology 2000-02, Vol.278 (2), p.335-L343
• Main Authors: Zhu, Daling, Bousamra, Michael, II, Zeldin, Darryl C, Falck, John R, Townsley, Mary, Harder, David R, Roman, Richard J, Jacobs, Elizabeth R
• Format: Article
• Language: English
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - pharmacology; Amides - pharmacology; Animals; Arachidonic Acid - metabolism; Cytochrome P-450 Enzyme System - metabolism; Dogs; In Vitro Techniques; Male; Pressure; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Rabbits; Vasoconstriction; Vasoconstrictor Agents - pharmacology; Vasomotor System - drug effects
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2000.278.2.L335

1  Department of Physiology, Cardiovascular Research Center, 6  Department of Medicine, and 2  Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; 4  Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235; 5  Department of Physiology, University of South Alabama, Mobile, Alabama 36688; and 3  Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Park, North Carolina 27709 Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5,6-, 8,9-, 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10 5 M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N -methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse-phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone. cytochrome P -450; pulmonary vascular tone; vasodilator; eicosanoid metabolism; arachidonic acid