Potent constriction of cat coronary arteries by hydroperoxides of arachidonic acid and its blockade by anti-inflammatory agents.
The omega-6 and omega-9 hydroperoxides of arachidonic acid caused dose-dependent constriction of cat coronary arteries in concentrations of 10(-8) to 10(-5) M. Their potency was comparable to that of prostaglandin (PG) E2, and PGF2 alpha and 100 times greater than that of arachidonic acid. The cyclooxygenase inhibitor, meclofenamate markedly reduced constriction caused by the hydroperoxides but potentiated constriction caused by the prostaglandins. The effects of the hydroperoxides were also reduced by indomethacin and dexamethasone but were unaffected by the thromboxane synthetase inhibitor imidazole. Since the hydroperoxides are not substrates for cyclooxygenase, it is suggested that they have a direct effect on the arteries which can be antagonized by anti-inflammatory drugs.
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D066298:In Vitro Techniques; D015289:Leukotrienes; D008054:Lipid Peroxides; D008469:Meclofenamic Acid / Q000494:pharmacology*; D010477:Perfusion; D010545:Peroxides / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D001095:Arachidonic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D010545:Peroxides; D011458:Prostaglandins E; D011460:Prostaglandins F; D014662:Vasoconstrictor Agents; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; C021201:12-HPETE; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D003907:Dexamethasone