Nitric oxide regulation of autonomic function in heart failure

Nitric oxide (NO) functions at all levels of the autonomic nervous system to influence sympathetic and parasympathetic control of cardiovascular function. It modulates the excitability of peripheral sensory and motor neurons of cardiovascular reflexes and the central neurons that integrate their function. Its effects within this system are diverse and site specific and are (at many levels) not well defined. However, most evidence suggests that the neuromodulator's influence acts to restrain sympathetic outflow and facilitate parasympathetic outflow. In chronic heart failure, these functional effects of NO are impaired or downregulated and contribute to the state of sympathetic overactivation and parasympathetic deactivation characterized by the disease. The cellular and molecular mechanisms regulating NO production and signaling in the autonomic nervous system in the normal and chronic heart failure state are summarized and discussed in light of their therapeutic implications. This review also emphasizes questions of regulation of NO function in the autonomic nervous system that remain unresolved.