The influence of endothelium-derived nitric oxide on myocardial contractile function.
Nitric oxide released by cardiac endothelial cells modulates myocardial contractile function through elevation of intracellular 3',5'-cyclic guanosine monophosphate (cGMP). In the absence of agonist stimulation, nitric oxide typically enhances myocardial relaxation and reduces diastolic tone, without significantly altering the rate of force or pressure development. This pattern of effect is observed with nitric oxide or with cGMP analogues in isolated rat cardiac myocytes, isolated ferret papillary muscle preparations, and isolated ejecting guinea-pig hearts. In human subjects studied at cardiac catheterisation, low-dose bicoronary infusions of sodium nitroprusside or of substance P induce similar effects on left ventricular systolic and diastolic function. These changes may benefit from cardiac filling and coronary perfusion by increasing the diastolic interval, reducing extravascular compressive forces and increasing the driving pressure for filling, e.g., during exercise. Nitric oxide may also modulate inotropic and chronotropic responses to beta-adrenergic stimulation. Under pathological conditions, overproduction of nitric oxide by an inducible nitric oxide synthase may be detrimental for contractile function. Dysfunction of the constitutive nitric oxide pathway could also contribute to pathophysiology, e.g., in conditions characterised by diastolic dysfunction. The paracrine nitric oxide pathway is likely to be an important regulator of cardiac contractile function, acting in concert and interacting with other regulatory pathways.
Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
A M
AM
Shah
B D
BD
Prendergast
R
R
Grocott-Mason
M J
MJ
Lewis
W J
WJ
Paulus
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005289:Ferrets; D006168:Guinea Pigs; D006801:Humans; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D051381:Rats
D009569:Nitric Oxide; D006152:Cyclic GMP