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(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.
Alam
M S
MS
First Department of Surgery, Shimane Medical University, Izumo, Japan.
Ku
K
K
Yamauchi
M
M
Hashimoto
M
M
Nosaka
S
S
Hossain
M S
MS
Masumura
S
S
Nakayama
K
K
Tamura
K
K
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009536:Niacinamide; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D015237:Dinoprost; D006861:Hydrogen Peroxide; D001920:Bradykinin; C042625:nicaraven; D004121:Dimethyl Sulfoxide