Abstract

Heart failure is characterized by an elevation in sympathetic tone. The mechanisms responsible for this sympatho-excitation of heart failure are not completely understood. Several studies from this laboratory have compared differences in the cardiac "sympathetic afferent" reflex between sham dogs and dogs with pacing-induced heart failure. We found 1) that the cardiac sympathetic afferent reflex is augmented in heart failure, 2) tonic cardiac sympathetic afferent inputs play an important role in the elevated sympathetic tone in heart failure, 3) cardiac sympathetic afferents are sensitized in heart failure and 4) the central gain of the cardiac sympathetic afferent reflex in heart failure is sensitized and that this sensitization may be related to augmented central Ang II and blunted NO mechanisms. These studies integrate into the regulation of sympathetic outflow in heart failure which is likely to be mediated by a variety of peripheral inputs modulated by central substances. If the cardiac sympathetic afferent reflex is one of the excitatory reflexes which contribute to sympathetic activation in heart failure, a comprehensive understanding of neuro-humoral regulation of this reflex may result in more definitives and rational therapy targeted to the sympathetic nervous system in this disease state.

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