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.