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The influence of endothelium-derived nitric oxide on myocardial contractile function
A M Shah1, B D Prendergast, R Grocott-Mason
1Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Insights
Nitric oxide (NO) enhances heart muscle relaxation and reduces diastolic tone by increasing cyclic guanosine monophosphate (cGMP). This NO-cGMP pathway is crucial for regulating cardiac function, both in normal physiology and disease.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Biomedical Science
Background:
- Cardiac endothelial cells release nitric oxide (NO), modulating myocardial contractile function.
- NO elevates intracellular 3',5'-cyclic guanosine monophosphate (cGMP), influencing cardiac performance.
- The NO-cGMP pathway plays a role in both physiological regulation and pathological conditions of the heart.
Purpose of the Study:
- To investigate the role of nitric oxide in modulating myocardial contractile function.
- To explore the effects of NO and cGMP on cardiac relaxation and diastolic tone.
- To examine the impact of NO on cardiac function in various experimental models and human subjects.
Main Methods:
- Experiments using isolated rat cardiac myocytes, ferret papillary muscle, and guinea-pig hearts.
- Administration of NO donors and cGMP analogues.
- Cardiac catheterization studies in human subjects with bicoronary infusions of sodium nitroprusside or substance P.
Main Results:
- NO and cGMP analogues enhance myocardial relaxation and reduce diastolic tone without significantly altering force or pressure development.
- Similar effects were observed in isolated cardiac preparations and in human subjects.
- NO influences inotropic and chronotropic responses to beta-adrenergic stimulation.
Conclusions:
- The paracrine nitric oxide pathway is a key regulator of cardiac contractile function.
- NO-cGMP signaling is important for cardiac relaxation and diastolic function.
- Dysregulation of NO pathways can contribute to cardiac pathophysiology, including diastolic dysfunction.
Abstract:
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.