title: Nitric oxide synthase regulation of cardiac excitation-contraction coupling in health and disease.
abstract: Significant advances in our understanding of the ability of nitric oxide synthases (NOS) to modulate cardiac function have provided key insights into the role NOS play in the regulation of excitation-contraction (EC) coupling in health and disease. Through both cGMP-dependent and cGMP-independent (e.g. S-nitrosylation) mechanisms, NOS have the ability to alter intracellular Ca(2+) handling and the myofilament response to Ca(2+), thereby impacting the systolic and diastolic performance of the myocardium. Findings from experiments using nitric oxide (NO) donors and NOS inhibition or gene deletion clearly implicate dysfunctional NOS as a critical contributor to many cardiovascular disease states. However, studies to date have only partially addressed NOS isoform-specific effects and, more importantly, how subcellular localization of NOS influences ion channels involved in myocardial EC coupling and excitability. In this review, we focus on the contribution of each NOS isoform to cardiac dysfunction and on the role of uncoupled NOS activity in common cardiac disease states, including heart failure, diabetic cardiomyopathy, ischemia/reperfusion injury and atrial fibrillation. We also review evidence that clearly indicates the importance of NO in cardioprotection. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System".
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
authors.forename: Jillian N
authors.initials: JN
authors.lastname: Simon
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
authors.forename: Drew
authors.initials: D
authors.lastname: Duglan
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Casadei
authors.affiliation: Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK. Electronic address: Ricardo.carnicer@cardiov.ox.ac.uk.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carnicer
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000378:metabolism*; D056966:Excitation Contraction Coupling / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D019001:Nitric Oxide Synthase
keywords: Arrhythmia; Heart failure; Ischemia/reperfusion; Microdomain; Myocardial function; Preconditioning