Recently, we have reported that a new synthetic compound, 1,2bis(nicotinamido)-propane (
nicaraven), improved cardiac function following preservation and reperfusion. In this study, we investigated the efficacy of
nicaraven as a radical scavenger by using an in vitro model of oxidative stress, to clarify mechanisms of the protective effect of this new compound on
reperfusion injury in rat heart. Ring segments of epicardial right coronary arteries (RCA) of pig were suspended in organ chambers and exposed to
hydroxyl radicals (.
OH), generated (by two different systems) by 0.28 mM FeSO4/0.28 mM H2O2 and DHF/Fe3+-
ADP (2.4 mM, 43 nM, and 1.56 uM, respectively) to the bathing
solution for 60 min. Prior exposure of the coronary arteries to .
OH significantly produced right-ward shift of the dose-response curves of the
bradykinin-induced endothelium-dependent relaxations (an increase in the ED50 value for
bradykinin by 4.37 and 1.98 times than control in two different .
OH generating systems, respectively), but did not affect the maximum relaxation responses. The presence of
nicaraven (10(-4) and 10(-5) M) in the .
OH generating system, shifted the dose-response 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 protective effect on
hydroxyl radical-induced endothelial dysfunctions of pig coronary artery.