Inhibition of lipoxygenase and cyclooxygenase augments cardiac injury by H2O2.
The role of arachidonic acid metabolites in the cardiac effects of toxic oxygen metabolites (TOM) was investigated in buffer-perfused rat hearts (Langendorff model). Hydrogen peroxide (H2O2, 200 microM) was given for 10 min to generate TOM, followed by 30 min recovery. H2O2 reduced left ventricular developed pressure (LVDP), increased left ventricular end-diastolic pressure (LVEDP), and increased coronary flow (CF). The hydroxyl radical scavenger thiourea inhibited the H2O2-induced effects. Perfusion with three lipoxygenase inhibitors, AA861, BWA4C, and diethylcarbamazine, in addition to H2O2, augmented the decrease of LVDP and the increase of LVEDP induced by H2O2. The cyclooxygenase inhibitor indomethacin had the same effects. The H2O2-induced increase in CF was not influenced by diethylcarbamazine, but inhibited by all other drugs. Control perfusion with drugs alone did not influence cardiac function. In conclusion, inhibition of lipoxygenase and cyclooxygenase augmented the depression of cardiac function induced by TOM. Leukotrienes and prostanoids appear to be protective against H2O2-induced cardiac injury.
Valen
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G
Department of Surgery, University of Tromsø, Norway.
Semb
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AG
Vaage
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J
D000818:Animals; D044482:Benzeneacetamides; D016227:Benzoquinones / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004049:Diethylcarbamazine / Q000494:pharmacology; D016166:Free Radical Scavengers; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology
D044482:Benzeneacetamides; D016227:Benzoquinones; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; C056614:N-(3-phenoxycinnamyl)acetohydroxamic acid; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D006861:Hydrogen Peroxide; D013890:Thiourea; D004049:Diethylcarbamazine; D007213:Indomethacin