The pharmacological activity of nitroxyl: a potent vasodilator with activity similar to nitric oxide and/or endothelium-derived relaxing factor.
Chemical oxidation of N-hydroxy-L-arginine (NOHA) and other N-hydroxyguanidines has been previously shown to generate either nitric oxide (NO) or nitroxyl (HNO), depending on the oxidative conditions. Because N-hydroxy-L-arginine has been demonstrated to be a biosynthetic intermediate in the oxidative conversion of arginine to endothelium-derived relaxing factor, the possible formation of HNO through a biological process was considered. This study, therefore, explores the biological activity of HNO as a possible effector molecule, and the results indicate that HNO is capable of eliciting vasorelaxation in both rabbit aorta and bovine intrapulmonary artery by a guanylate cyclase-dependent pathway. The pharmacological properties of HNO were very similar to those of endothelium-derived relaxing factor, and the possible relationship between HNO and endothelium-derived relaxing factor is discussed.
Fukuto
J M
JM
Department of Pharmacology, UCLA School of Medicine.
Chiang
K
K
Hszieh
R
R
Wong
P
P
Chaudhuri
G
G
D000818:Animals; D001011:Aorta; D002417:Cattle; D003484:Cyanamide / Q000737:chemistry; D006152:Cyclic GMP / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects; D008168:Lung / Q000098:blood supply; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000737:chemistry / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D009589:Nitrogen Oxides; D014665:Vasodilator Agents; D009569:Nitric Oxide; D003484:Cyanamide; C039900:nitroxyl; D006152:Cyclic GMP; D008751:Methylene Blue