title: Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.
abstract: The nitric oxide (NO(•)) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO(•) as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic" nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure.
authors.affiliation: Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Carlo G
authors.initials: CG
authors.lastname: Tocchetti
authors.forename: Brian A
authors.initials: BA
authors.lastname: Stanley
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Murray
authors.forename: Vidhya
authors.initials: V
authors.lastname: Sivakumaran
authors.forename: Sonia
authors.initials: S
authors.lastname: Donzelli
authors.forename: Daniele
authors.initials: D
authors.lastname: Mancardi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Wei Dong
authors.initials: WD
authors.lastname: Gao
authors.forename: Jennifer
authors.initials: J
authors.lastname: van Eyk
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
authors.forename: David A
authors.initials: DA
authors.lastname: Wink
authors.forename: Nazareno
authors.initials: N
authors.lastname: Paolocci
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D019001:Nitric Oxide Synthase; C039900:nitroxyl