Animals; Heart Rate/physiology; Mice; Mice, Knockout; Mice, Transgenic; Myocardial Contraction/physiology; Nitric Oxide Synthase/physiology; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III
Abstract :
[en] The modulatory role of endothelial nitric oxide synthase (eNOS) on heart contraction, relaxation and rate is examined in light of recent studies using genetic deletion or overexpression in mice under specific conditions. Unstressed eNOS-/- hearts in basal conditions exhibit a normal inotropic and lusitropic function, with either decreased or unchanged heart rate. Under stimulation with catecholamines, eNOS-/- mice predominantly show a potentiation in their beta-adrenergic inotropic and lusitropic responsiveness. A similar phenotype is observed in beta 3-adrenoceptor deficient mice, pointing to a key role of this receptor subtype for eNOS coupling. The effect of eNOS on the muscarinic cholinergic modulation of cardiac function probably operates in conjunction with other NO-independent mechanisms, the persistence of which may explain the apparent dispensability of this isoform for the effect of acetylcholine in some eNOS-/- mouse strains. eNOS-/- hearts submitted to short term ischaemia-reperfusion exhibit variable alterations in systolic and diastolic function and infarct size, while those submitted to myocardial infarction present a worsened ventricular remodelling, increased 1 month mortality and loss of benefit from ACE inhibitor or angiotensin II type I receptor antagonist therapy. Although non-conditional eNOS gene deletion may engender phenotypic adaptations (e.g. ventricular hypertrophy resulting from chronic hypertension, or upregulation of the other NOS isoforms) potentially confounding the interpretation of comparative studies, the use of eNOS-/- mice has undoubtedly advanced (and will probably continue to improve) our understanding of the complex role of eNOS (in conjunction with the other NOSs) in the regulation of cardiac function. The challenge is now to confirm the emerging paradigms in human cardiac physiology and hopefully translate them into therapy.
Disciplines :
Anesthesia & intensive care
Author, co-author :
MASSION, Paul ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
Balligand, J.-L.
Language :
English
Title :
Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice.
Publication date :
2003
Journal title :
Journal of Physiology
ISSN :
0022-3751
eISSN :
1469-7793
Publisher :
Blackwell Publishing, New York, United States - New York
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