Conversion of nitroxyl (HNO) to nitric oxide (NO) in biological systems: the role of physiological oxidants and relevance to the biological activity of HNO.
Nitroxyl (HNO) and nitric oxide (NO) are chemically related compounds in that NO is the one-electron oxidation product of HNO. Previous studies from this laboratory indicated that HNO elicits pharmacological effects that are similar to those elicited by NO, namely, vascular smooth muscle relaxation and stimulation of cyclic GMP formation. The objective of the present study was to determine whether HNO could be converted to NO under physiological conditions and thereby account for the pharmacological actions of HNO. Utilizing the method of chemiluminescence detection, HNO was found to be readily converted to NO by a variety of ubiquitous biological oxidants including oxygen, superoxide dismutase, methemoglobin and flavins. The potency of HNO as a vasorelaxant using isolated rabbit aortic rings was markedly increased 30-fold by superoxide dismutase, whereas the potency of the NO-donor compound, S-nitroso-N-acetylpenicillamine (SNAP), was increased only 2-fold. These data indicate that the ready conversion of HNO to NO may account for the biological activity of HNO. Thus, HNO and HNO-donor compounds represent good sources of NO.
Fukuto
J M
JM
Department of Pharmacology, UCLA School of Medicine, Center for the Health Sciences 90024-1735.
Hobbs
A J
AJ
Ignarro
L J
LJ
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D007700:Kinetics; D008163:Luminescent Measurements; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism*; D010101:Oxygen Consumption; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology*
D005609:Free Radicals; D009589:Nitrogen Oxides; D016877:Oxidants; D009569:Nitric Oxide; D013482:Superoxide Dismutase; C039900:nitroxyl