Cardiac neurobiology of nitric oxide synthases

Nitric oxide (NO) is a potent modulator of cardiac and vascular regulation. Its role in cardiac-autonomic neural signaling has received much attention over the last decade because of the ability of NO to alter cardiac sympathovagal balance to favor more anti-arrhythmic states. Complexity and controversy have arisen, however, because of the numerous sources of NO in the brain, peripheral nerves, and cardiomyocytes, all of which are potential regulators of cardiac excitability and calcium signaling. This review addresses the integrative role of NO as a relatively ubiquitous signaling molecule with respect to cardiac neurobiology. The present idea, that divergent NO-signaling pathways from multiple sources within the heart and nervous system converge to modulate cardiac excitability and impact on morbidity and mortality in health and disease, is discussed.