Novel mechanisms of sympatho-excitation in chronic heart failure.
Chronic heart failure (CHF) is associated with an increase in the production and secretion of various regulatory hormones that are initially beneficial, but become deleterious when elevated for prolonged periods. The neurohumoral excitation that occurs in the CHF state is mediated, in part, by abnormal inhibitory cardiovascular reflexes, such as the arterial baroreflex and the cardiopulmonary reflex. In addition, two sympatho-excitatory reflexes have been shown to be enhanced in CHF: the arterial chemoreflex and the cardiac sympathetic afferent reflex. While these reflexes may play a role in the sympatho-excitation of the CHF state, there is an important central modulation of sympathetic outflow by a variety of hormones that are elevated in CHF and have been shown to have neural effects. These include angiotensin II (Ang II), nitric oxide (NO), and endothelin-1. In fact, experimental animal data suggest that a central reciprocal relationship exists between Ang II and NO in their ability to modulate sympathetic outflow. These substances may also participate in the beneficial effects of exercise training in the CHF state. Exercise training lowers sympathetic nerve activity and plasma Ang II, and enhances arterial baroreflex function. This review emphasizes the neurohormonal and reflex regulation of sympathetic outflow in heart failure. While abnormal reflex regulation may predict a poor outcome, new treatment options may emerge from a better understanding of reflex regulation in CHF.
Zucker
Irving H
IH
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
Pliquett
Rainer U
RU
D000804:Angiotensin II / Q000378:metabolism; D017704:Baroreflex / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*
D019332:Endothelin-1; D000804:Angiotensin II; D009569:Nitric Oxide