allopurinol and Coronary-Vasospasm

In bovine coronary artery segments, peroxynitrite inhibits prostacyclin (PGI2) synthase by tyrosine nitration. Using this pharmacological model, we show that a 1 h exposure of bovine coronary artery segments to endotoxin (lipopolysaccharide [LPS]) inhibits the relaxation phase following angiotensin II (Ang II) stimulation and causes a vasospasm that can be suppressed by a thromboxane A2 (TxA2) receptor blocker. In parallel, PGI2 synthesis decreases in favor of prostaglandin E2 formation. Immunoprecipitation and costaining with an anti-nitrotyrosine antibody identified PGI2 synthase as the main nitrated protein in the endothelium. All effects of LPS could be prevented in the presence of the nitric oxide (NO) synthase inhibitor Nomega-mono-methyl-L-arginine and polyethylene-glycolated Cu/Zn- superoxide dismutase. Thus, the early phase of endothelial cell activation in bovine coronary arteries by inflammatory agents proceeds by a protein synthesis-independent priming process for a source of superoxide that we tentatively attribute to xanthine oxidase. Upon receptor activation, Ang II stimulates NO and superoxide production, resulting in a peroxynitrite-mediated nitration and inhibition of PGI2 synthase. The remaining 15-hydroxy-prostaglandin 9,11-endoperoxide (PGH2) first activates the TxA2/PGH2 receptor and then is converted to prostaglandin E2 (PGE2) by smooth muscle cells. PGE2 together with a lack of NO and PGI2 is known to promote the adhesion of white blood cells and their immigration to the inflammatory locus.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin II; Animals; Cattle; Coronary Vasospasm; Coronary Vessels; Cytochrome P-450 Enzyme System; Endothelium, Vascular; In Vitro Techniques; Intramolecular Oxidoreductases; Lipopolysaccharides; Nitrates; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Peroxynitrous Acid; Polyethylene Glycols; Prostaglandin Endoperoxides; Receptors, Thromboxane; Superoxide Dismutase; Superoxides; Vasoconstriction; Vasodilation; Xanthine Oxidase

The effects of oxygen free radicals on coronary vasoreactivity remain unknown.. To examine whether oxygen free radicals increase coronary arterial tone and sensitivity to vasoconstrictor stimulation in closed-chest dogs.. Oxygen radicals were generated by the reaction of xanthine plus xanthine oxidase (XXO) and effects of these substances on the left coronary artery (the percentage diameter change) and on the constrictor effect of ergonovine were examined in vivo in 19 anesthetized, closed-chest dogs by selective coronary angiography. The effects of XXO solution and ergonovine were assessed in a cumulative fashion using 100, 200, and 300 ml XXO and 50, 100, 150, and 200 micrograms ergonovine, in 5 (group I) and 6 dogs (group II), respectively. The effects of XXO on the constrictor responses elicited by 50 micrograms ergonovine were examined in eight dogs (group III). Changes in the vascular endothelium were examined by postmortem electron microscopic examination.. Oxidative injury alone produced slight constriction of the coronary artery, but the change was not significant. However, ergonovine-induced vasoconstriction was enhanced after administration of 100 and 200 ml (cumulative amount) XXO solution (P < 0.05, group II versus group III). The enhancement was no longer observed after administration of 300 ml (cumulative amount) XXO solution. Scanning and transmission electron microscopies revealed the formation of blebs and ulceration in the coronary endothelium after administration of XXO solution.. These results suggest that oxygen radicals can enhance the ergonovine-induced coronary vasoconstriction in a concentration-dependent manner. There seems to be a critical level of oxygen radicals for the production of the effect.

Topics: Animals; Coronary Angiography; Coronary Vasospasm; Coronary Vessels; Dogs; Endothelium, Vascular; Ergonovine; Microscopy, Electron; Microscopy, Electron, Scanning; Reactive Oxygen Species; Vasoconstrictor Agents; Xanthine; Xanthine Oxidase; Xanthines

Topics: Allopurinol; Anaphylaxis; Coronary Vasospasm; Drug Interactions; Emergencies; Enalapril; Humans; Male; Middle Aged; Myocardial Infarction