INCREASING VASOCONSTRICTOR RESPONSE TO ERGONOVINE WITH OXIDATIVE INJURY IN CANINE CORONARY-ARTERY

Background The effects of oxygen free radicals on coronary vasoreactiv ity remain unknown, Objective To examine whether oxygen free radicals increase coronary arterial tone and sensitivity to vasoconstrictor sti mulation in closed-chest dogs. Methods 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 angio graphy. The effects of XXO solution and ergonovine were assessed in a cumulative fashion using 100, 200, and 300 mi XXO and 50, 100, 150, an d 200 mu g ergonovine, in 5 (group I) and 6 dogs (group II), respectiv ely. The effects of XXO on the constrictor responses elicited by 50 mu g ergonovine were examined in eight dogs (group III), Changes in the vascular endothelium were examined by postmortem electron microscopic examination, Results Oxidative injury alone produced slight constricti on of the coronary artery, but the change was not significant, However , ergonovine-induced vasoconstriction was enhanced after administratio n of 100 and 200 mi (cumulative amount) XXO solution (P<0.05, group II versus group III), The enhancement was no longer observed after admin istration of 300 mi (cumulative amount) XXO solution. Scanning and tra nsmission electron microscopies revealed the formation of blebs and ul ceration in the coronary endothelium after administration of XXO solut ion. Conclusion These results suggest that oxygen radicals can enhance the ergonovine-induced coronary vasoconstriction in a concentration-d ependent manner. There seems to be a critical level of oxygen radicals for the production of the effect.