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(Circulation. 2001;104:2260.)
© 2001 American Heart Association, Inc.

Editorials

Nitric Oxide and Cardiac Contractility in Human Heart Failure

Time for Reappraisal

Walter J. Paulus, MD PhD; Stefan Frantz, MD; Ralph A. Kelly, MD

From the Cardiovascular Center, O.L.V. Ziekenhuis, Aalst, Belgium (W.J.P.); the Medizinische Universitätsklinik Würzburg, Würzburg, Germany (S.F.); and the Genzyme Corporation, Framingham, Mass (R.A.K.).

Correspondence to Walter J. Paulus, MD, PhD, Cardiovascular Center, O.L.V. Ziekenhuis, Moorselbaan 164, B 9300 Aalst, Belgium. E-mail walter.paulus@pi.be

Key Words: Editorials • nitric oxide synthase • heart failure • nitric oxide • myocardial contraction

The free radical gas nitric oxide (NO) is produced by 3 isoforms of nitric oxide synthase (NOS). All of them are present in the heart: NOS1 (nNOS, "neuronal" NOS) has been detected in cardiac conduction tissue and intracardiac neurons; NOS2 (iNOS, "cytokine-inducible" NOS) can be expressed by virtually all cells in the heart, often in conjunction with the expression of inflammatory cytokines; and finally, NOS3 (eNOS, "endothelial-constitutive" NOS) is expressed in coronary endothelium, endocardium, and cardiac myocytes. NOS3 regulates the tone of vascular smooth muscle cells; the permeability and platelet adhesion of endothelial cells; and the receptor-effector coupling, energetics, contractility, and apoptosis of cardiomyocytes.^1,2 Since the original demonstration of myocardial NOS2 activity in idiopathic dilated cardiomyopathy,³ a negative inotropic effect of NO frequently was hypothesized to contribute to the depressed contractile function of failing myocardium. This hypothesis was inspired by the simultaneous publication of experimental results that showed a depressed contractile response of isolated cardiomyocytes to ß-adrenergic agonists after NOS2 induction by lipopolysaccharides.⁴

See p 2318

To further explore this depressant action of NO on myocardial contractility, numerous experimental and clinical studies were performed, but they yielded apparently conflicting results on the inotropic effect of NO from either endogenous or pharmacological sources.² As reported in this issue of Circulation, Cotton et al⁵ tackled the question of the inotropic action of NO by measuring left ventricular (LV) performance in normal control subjects and in patients with dilated cardiomyopathy during intracoronary infusion of the NOS inhibitor N^G-monomethyl-L-arginine (L-NMMA). . . . [Full Text of this Article]

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