New insights of heart rate modulation: involvement of cardiac nitric oxide.

FELLET A.; ARRANZ C; BALASZCZUK A.

Free Radical Pathophysiology. Section 2: Mitochondria in Patophysiology.

Transworld Research Network

Lugar: Kerala, India; Año: 2008; p. 37 - 52

Emerging evidence supports the notion that alterations in autonomic control and myocardial NO production are linked to the development and progression of heart failure. Focusing on autonomic control of heart rate, the complexity of the actions of NO at distinct levels throughout the autonomic nervous system and its relationship with other modulators can be demonstrated. Despite its high diffusivity and the apparent abundance of potential targets, the effects on NO-mediated systems are selective in the heart. It is clear that, given the multiple and opposite actions of NO on cardiac control, interpretation of a response after a global intervention of the NO system (e.g. systemic administration of SNP, L-NAME or a NOS isoform knockout), will be difficult. The diversity of the intracellular pathways activated by NO and their differential sensitivity to different levels of NO might account for some aspects of specific and opposite effects. There are several plausible mechanisms that might account for this specificity in the context of autonomic regulation of heart rate. NO acts at different levels within the autonomic nervous system to control cardiac rate, with opposite effects at different sites. We will discuss factors that might contribute to this diversity of action, and the effects of NO on ATP generation and/or metabolic pathways that may be attractive targets of novel therapeutic strategies aimed to the prevention or early treatment of heart failure.