PROTECTIVE EFFECTS OF NICARAVEN, A NEW HYDROXYL RADICAL SCAVENGER ON THE ENDOTHELIAL DYSFUNCTION AFTER EXPOSURE OF PIG CORONARY-ARTERY TO HYDROXYL RADICALS

Recently, we have reported that a new synthetic compound, 1,2bis(nicot inamido)-propane (nicaraven), improved cardiac function following pres ervation and reperfusion. In this study, we investigated the efficacy of nicaraven as a radical scavenger by using an in vitro model of oxid ative stress, to clarify mechanisms of the protective effect of this n ew compound on reperfusion injury in rat heart. Ring segments of epica rdial right coronary arteries (RCA) of pig were suspended in organ cha mbers and exposed to hydroxyl radicals ((OH)-O-.), generated (by two d ifferent systems) by 0.28 mM FeSO4/0.28 mMH(2)O(2) and DHF/Fe3+-ADP (2 .4 mM, 43 nM, and 1.56 uM, respectively) to the bathing solution for 6 0 min. Prior exposure of the coronary arteries to (OH)-O-. significant ly produced right-ward shift of the dose-response curves of the bradyk inin-induced endothelium-dependent relaxations (an increase in the ED5 0 value for bradykinin by 4.37 and 1.98 times than control in two diff erent (OH)-O-. generating systems, respectively), but did not affect t he maximum relaxation responses. The presence of nicaraven (10(-4) and 10(-5) M) in the (OH)-O-. generating system, shifted the dose-respons e curves to bradykinin to the control level, suggesting a significant hydroxyl radical scavenging effect of the drug. These results indicate that nicaraven, a new hydroxyl radical scavenger, exhibits a protecti ve effect on hydroxyl radical-induced endothelial dysfunctions of pig coronary artery.