Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component?
Nitric oxide (NO) has been shown to regulate cardiac function, both in physiological conditions and in disease states. However, several aspects of NO signalling in the myocardium remain poorly understood. It is becoming increasingly apparent that the disparate functions ascribed to NO result from its generation by different isoforms of the NO synthase (NOS) enzyme, the varying subcellular localization and regulation of NOS isoforms and their effector proteins. Some apparently contrasting findings may have arisen from the use of non-isoform-specific inhibitors of NOS, and from the assumption that NO donors may be able to mimic the actions of endogenously produced NO. In recent years an at least partial explanation for some of the disagreements, although by no means all, may be found from studies that have focused on the role of the neuronal NOS (nNOS) isoform. These data have shown a key role for nNOS in the control of basal and adrenergically stimulated cardiac contractility and in the autonomic control of heart rate. Whether or not the role of nNOS carries implications for cardiovascular disease remains an intriguing possibility requiring future study.
Sears
Claire E
CE
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Ashley
Euan A
EA
Casadei
Barbara
B
D001341:Autonomic Nervous System / Q000502:physiology; D017704:Baroreflex / Q000502:physiology; D001693:Biological Transport, Active / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D015398:Signal Transduction / Q000502:physiology*
D007527:Isoenzymes; D009569:Nitric Oxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I