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(Circulation. 2005;112:2293-2300.)
© 2005 American Heart Association, Inc.

Heart Failure

Mechanoreflex Mediates the Exaggerated Exercise Pressor Reflex in Heart Failure

Scott A. Smith, PhD; Jere H. Mitchell, MD; R. Haris Naseem, MD; Mary G. Garry, PhD

From the Departments of Internal Medicine (J.H.M., R.H.N., M.G.G.), Physiology (J.H.M.), and Health Care Sciences (S.A.S.), Harry S. Moss Heart Center, University of Texas Southwestern Medical Center, Dallas.

Correspondence to Mary G. Garry, PhD, University of Texas Southwestern Medical Center, Harry S. Moss Heart Center, Department of Internal Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390-9174. E-mail mary.garry{at}utsouthwestern.edu

Received June 3, 2005; revision received July 19, 2005; accepted July 25, 2005.

Background— In heart failure, exercise elicits excessive increases in mean arterial pressure (MAP) and heart rate (HR). Using a novel rat model, we previously demonstrated that this exaggerated cardiovascular responsiveness is mediated by an overactive exercise pressor reflex (EPR). Although we previously determined that abnormalities in the group IV afferent neuron population (associated with the metabolic component of the reflex) initiate the development of the exaggerated EPR in heart failure, these fibers do not mediate the enhanced circulatory responses to exercise. Therefore, we hypothesized that the augmentation in EPR activity is primarily mediated by the mechanically sensitive component of the reflex (mediated predominately by activation of group III afferent fibers).

Methods and Results— Male Sprague-Dawley rats were divided into 3 groups: sham (control), dilated cardiomyopathic (DCM), and neonatal capsaicin-treated animals (NNCAP, group IV afferent fibers ablated). Activation of the EPR by electrically induced static muscle contraction of the hindlimb resulted in larger increases in MAP and HR in DCM and NNCAP compared with sham animals. In all groups, administration of gadolinium (a selective blocker of mechanically sensitive receptors) within the hindlimb attenuated the MAP and HR responses to contraction. However, the magnitude of this reduction was greater in DCM and NNCAP compared with sham animals.

Conclusions— From these data, we conclude that the muscle mechanoreflex mediates the exaggerated EPR that develops in heart failure. Moreover, these findings suggest that mechanoreflex overactivity in heart failure may be a compensatory response to functional alterations in group IV fibers. Given these findings, the muscle mechanoreflex may serve as a novel target in the treatment of the abnormal circulatory responses to exercise in heart failure.

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