title: Nitric oxide's role in the heart: control of beating or breathing?
abstract: Beneficial actions of nitric oxide (NO) in failing myocardium have frequently been overshadowed by poorly documented negative inotropic effects mainly derived from in vitro cardiac preparations. NO's beneficial actions include control of myocardial energetics and improvement of left ventricular (LV) diastolic distensibility. In isolated cardiomyocytes, administration of NO increases their diastolic cell length consistent with a rightward shift of the passive length-tension relation. This shift is explained by cGMP-induced phosphorylation of troponin I, which prevents calcium-independent diastolic cross-bridge cycling and concomitant diastolic stiffening of the myocardium. Similar improvements in diastolic stiffness have been observed in isolated guinea pig hearts, in pacing-induced heart failure dogs, and in patients with dilated cardiomyopathy or aortic stenosis and have been shown to result in higher LV preload reserve and stroke work. NO also controls myocardial energetics through its effects on mitochondrial respiration, oxygen consumption, and substrate utilization. The effects of NO on diastolic LV performance appear to be synergistic with its effects on myocardial energetics through prevention of myocardial energy wastage induced by LV contraction against late-systolic reflected arterial pressure waves and through prevention of diastolic LV stiffening, which is essential for the maintenance of adequate subendocardial coronary perfusion. A drop in these concerted actions of NO on diastolic LV distensibility and on myocardial energetics could well be instrumental for the relentless deterioration of failing myocardium.
authors.affiliation: Institute for Cardiovascular Research, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. wj.paulus@vumc.nl
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Jean G F
authors.initials: JG
authors.lastname: Bronzwaer
mesh_terms: D000818:Animals; D003971:Diastole; D004734:Energy Metabolism; D006321:Heart / Q000502:physiology* / Q000503:physiopathology*; D006801:Humans; D007537:Isometric Contraction; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D009569:Nitric Oxide