TY - JOUR
T1 - Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries
AU - Zhu, Daling
AU - Bousamra, Michael
AU - Zeldin, Darryl C.
AU - Falck, J R
AU - Townsley, Mary
AU - Harder, David R.
AU - Roman, Richard J.
AU - Jacobs, Elizabeth R.
PY - 2000/2
Y1 - 2000/2
N2 - 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, CYPIA, 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.
AB - 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, CYPIA, 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.
KW - Arachidonic acid
KW - Cytochrome P-450
KW - Eicosanoid metabolism
KW - Pulmonary vascular tone
KW - Vasodilator
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U2 - 10.1152/ajplung.2000.278.2.l335
DO - 10.1152/ajplung.2000.278.2.l335
M3 - Article
C2 - 10666118
AN - SCOPUS:0034014269
SN - 1040-0605
VL - 278
SP - L335-L343
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 2 22-2
ER -