Key result
Endothelial and neuronal nitric oxide synthase isoforms maintain autonomic balance and Frank-Starling adaptation in the heart, while inducible NOS may become maladaptive as cardiac disease progresses.
This review highlights the compartment-specific signaling of endogenous nitric oxide synthase isoforms in regulating cardiac excitation-contraction coupling and autonomic balance.
Hypothesis-generating for isoform-selective NOS modulation in HF; prospective trials needed before clinical translation.
The role of nitric oxide (NO) as a regulator of cardiac contraction was suggested in the early nineties, but a consensual view of its main functions in cardiac physiology has only recently emerged with the help of experiments using genetic deletion or overexpression of the three nitric oxide synthase (NOS) isoforms in cardiomyocytes. Contrary to the effects of exogenous, pharmacologic NO donors, signaling by endogenous NO is restricted to intracellular effectors co-localized with NOS in specific subcellular compartments. This both ensures coordinate signaling by the three NOS isoforms on different aspects of the cardiomyocyte function and helps to reconcile previous apparently contradictory observations based on the use of non-isoform-specific NOS inhibitors. This review will emphasize the role of NOS on excitation-contraction coupling in the normal and diseased heart. Endothelial NOS and neuronal NOS contribute to maintain an adequate balance between adrenergic and vagal input to the myocardium and participate in the early and late phases of the Frank-Starling adaptation of the heart. At the early phases of cardiac diseases, inducible NOS reinforces these effects, which may become maladaptive as disease progresses.
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Belge et al. (2005) conducted a review in Cardiac physiology and disease. Nitric oxide and nitric oxide synthase (NOS) isoforms was evaluated. Endothelial and neuronal nitric oxide synthase isoforms maintain autonomic balance and Frank-Starling adaptation in the heart, while inducible NOS may become maladaptive as cardiac disease progresses.
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