Novel Pathogenetic Mechanisms in Myocarditis: Nitric Oxide Signaling

The nitric oxide (NO) signaling pathway plays important roles in the regulation of most organ systems, participating in physiologic regulation and pathophysiologic organ dysfunction. Physiologic NO signaling is mediated by the precise subcellular localization of NO synthases (NOS) in proximity to target effector molecules. Organ dysfunction can occur by NOS downregulation, loss of spatial localization, or the induction of high-output NOS isoforms, such as calcium-independent NOS, leading to nitrosative stress. Myocarditis represents a prototypic clinical scenario for the dysregulation of NOS isoforms within the heart. This article reviews the physiologic roles for neuronal and endothelial NOS in cardiac function and the various consequences of spatial regulation of NOS informs and calcium-independent NOS induction, which influences organ function, antiviral immunity, and apoptosis.