Involvement of nitroxyl (HNO) in the cyanamide-induced vasorelaxation of rabbit aorta.
Relaxation of precontracted rabbit aortic rings in vitro by cyanamide, a clinically used alcohol deterrent drug, required catalase and H2O2, suggesting that a bioactivation mechanism was involved. Since the oxidation of cyanamide by catalase/H2O2 had been shown previously to lead to nitroxyl (HNO) generation via the intermediate N-hydroxycyanamide, and aortic ring relaxation was inhibited by the catalase inhibitor, 3-aminotriazole, HNO appears to be responsible for the vasorelaxation mediated by cyanamide. This was further supported by the observation that N,O-dibenzoyl-N-hydroxycyanamide (DBHC), a derivative of N-hydroxycyanamide that releases HNO in the absence of catalase/H2O2, was a potent vasorelaxant, with an EC50 of 4.2 +/- 1.3 x 10(-6) M.
Fukuto
J M
JM
Department of Pharmacology, UCLA School of Medicine 90024-1735.
Gulati
P
P
Nagasawa
H T
HT
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D003484:Cyanamide / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D005609:Free Radicals; D009589:Nitrogen Oxides; D003484:Cyanamide; D002374:Catalase; C039900:nitroxyl