Orthogonal properties of the redox siblings nitroxyl and nitric oxide in the cardiovascular system: a novel redox paradigm

1 Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; 2 Department of Chemistry, University of Arizona, Tucson, Arizona 85721; 3 Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287; 4 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130; 5 Division of Neurology, Duke University Medical Center, Durham, North Carolina 27710; 6 Department of Molecular and Medical Pharmacology, Center for the Health Sciences, University of California, Los Angeles, California 90095; and 7 Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, 10041 Orbassano, Italy Submitted 6 June 2003 ; accepted in final form 3 July 2003 Endogenous formation of nitric oxide (NO) and related nitrogen oxides in the vascular system is critical to regulation of multiple physiological functions. An imbalance in the production or availability of these species can result in progression of disease. Nitrogen oxide research in the cardiovascular system has primarily focused on the effects of NO and higher oxidation products. However, nitroxyl (HNO), the one-electron-reduction product of NO, has recently been shown to have unique and potentially beneficial pharmacological properties. HNO and NO often induce discrete biological responses, providing an interesting redox system. This article discusses the emerging aspects of HNO chemistry and attempts to provide a framework for the distinct effects of NO and HNO in vivo. guanosine 3',5'-cyclic monophosphate; calcitonin gene-related peptide; Angeli's salt Address for reprint requests and other correspondence: D. A. Wink, Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. B3-B69, Bethesda, MD 20892 (E-mail: wink{at}box-w.nih.gov ).