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Epoxyeicosatrienoic Acid‐Induced Pulmonary Vasoconstriction is Mediated by Prostacyclin‐Induced Thromboxane‐Receptor Activation
Author(s) -
Procknow Jesse D,
Le Duy,
Sprague Randy S,
Stephenson Alan H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1150.10
Subject(s) - prostacyclin , contraction (grammar) , thromboxane a2 , vasoconstriction , hypoxic pulmonary vasoconstriction , thromboxane , chemistry , cyclooxygenase , medicine , endocrinology , thromboxane receptor , prostaglandin h2 , prostaglandin , endothelium , receptor , receptor antagonist , vasodilation , epoxyeicosatrienoic acid , antagonist , arachidonic acid , biochemistry , enzyme , platelet
Epoxyeicosatrienoic acids (EETs) were reported to contribute to the increased pulmonary artery (PA) pressure of hypoxia‐induced pulmonary hypertension. EET‐induced PA contraction requires vascular endothelium, cyclooxygenase‐1 (COX‐1) activity and activation of the thromboxane receptor (TP) but not thromboxane synthesis. Here, we show that prostacyclin (PGI 2 ) is a potential mediator of EET‐induced PA contraction. Incubation of rabbit intralobar PA rings with 5,6‐EET at its EC 50 for PA contraction (0.7 μM) increased PGI 2 synthesis by 2.5 ± 0.2 fold over baseline in an endothelium‐dependent manner. In isolated PA rings, incubation with SC‐560, a selective COX‐1 inhibitor, reduced 5,6‐EET‐induced PA contraction and PGI 2 synthesis > 95% (P<0.01). PGI 2 , but not 6‐keto‐PGF 1α , its breakdown product, contracted PA rings in a concentration‐dependent manner, but unlike 5,6‐EET, PGI 2 ‐induced contraction was independent of COX‐1 and endothelium. SQ 29,548 (1 μM), a selective TP receptor antagonist, reduced PGI 2 ‐induced PA contractions > 99% (P<0.01). PGI 2 ‐induced PA contraction was not inhibited by CAY10441 (10 μM), a selective inhibitor of the PGI 2 (IP) receptor. These results are consistent with the hypothesis that PGI 2 synthesized in the vascular endothelium mediates EET‐induced contraction of intralobar PA via TP‐receptor activation. Support: NIH HL64180, HL089094.