doi: 10.1161/01.CIR.0000162473.10951.0A
(Circulation. 2005;111:2056-2065.)
© 2005 American Heart Association, Inc.
Heart Failure |
The Capsaicin-Sensitive Afferent Neuron in Skeletal Muscle Is Abnormal in Heart Failure
From the Departments of Internal Medicine (M.A.W., J.H.M., P.P.A.M., M.G.G.), Physiology (J.H.M.), and Health Care Sciences (S.A.S.), Harry S. Moss Heart Center, and Donald W. Reynolds Cardiovascular Clinical Research Center (P.P.A.M.), University of Texas Southwestern Medical Center, Dallas.
Correspondence to Mary G. Garry, PhD, Department of Internal Medicine, Harry S. Moss Heart Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9174. E-mail mary.garry{at}utsouthwestern.edu
Received September 3, 2004; revision received November 11, 2004; accepted December 23, 2004.
Background— In heart failure, the cardiovascular response to activation of the skeletal muscle exercise pressor reflex (EPR) is exaggerated. Group IV afferent neurons, primarily stimulated by the metabolic by-products of skeletal muscle work, contribute significantly to the EPR. Therefore, it was postulated that alterations in the activity of group IV neurons contribute to the EPR dysfunction manifest in heart failure.
Methods and Results— Group IV afferent fibers were ablated in neonatal Sprague-Dawley rats by subcutaneous administration of capsaicin. In neonatal capsaicin-treated adult animals, selective activation of the EPR, by electrically induced static muscle contraction, recapitulated the exaggerated increases in heart rate and blood pressure observed in rats with dilated cardiomyopathy (DCM). Furthermore, compared with control animals, both neonatal capsaicin-treated and DCM rats displayed a decreased pressor response to the intra-arterial administration of capsaicin within the hindlimb, a maneuver that selectively excites group IV afferent neurons. Moreover, expression of mRNA for the capsaicin receptor TRPv1, a marker of group IV fibers, was downregulated in DCM animals compared with controls.
Conclusions— These findings suggest that EPR dysfunction in heart failure results in part from functional and molecular alterations in group IV fibers. Furthermore, the responsiveness of these metabolically sensitive neurons appears to be blunted in DCM, indicating that their contribution to the EPR may be reduced. This occurs despite an overall exaggeration of the EPR in heart failure. These insights into the basic mechanisms of EPR dysfunction are essential to the development of effective therapeutic strategies aimed at improving exercise capacity in heart failure.
Key Words: blood pressure • cardiomyopathy • exercise • heart failure • reflex
This article has been cited by other articles:
 |
|
 |
|
  M. A. Williams, S. A. Smith, D. E. O'Brien, J. H. Mitchell, and M. G. Garry The group IV afferent neuron expresses multiple receptor alterations in cardiomyopathyic rats: evidence at the cannabinoid CB1 receptor J. Physiol., February 1, 2008; 586(3): 835 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsukawa and T. Nakamoto Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia J Appl Physiol, January 1, 2008; 104(1): 82 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Koba, J. Xing, L. I. Sinoway, and J. Li Sympathetic nerve responses to muscle contraction and stretch in ischemic heart failure Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H311 - H321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Smith, M. A. Williams, A. K. Leal, J. H. Mitchell, and M. G. Garry Exercise pressor reflex function is altered in spontaneously hypertensive rats J. Physiol., December 15, 2006; 577(3): 1009 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koba, Z. Gao, J. Xing, L. I. Sinoway, and J. Li Sympathetic responses to exercise in myocardial infarction rats: a role of central command Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2735 - H2742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Augustyniak, E. J. Ansorge, J.-K. Kim, J. A. Sala-Mercado, R. L. Hammond, N. F. Rossi, and D. S. O'Leary Cardiovascular responses to exercise and muscle metaboreflex activation during the recovery from pacing-induced heart failure J Appl Physiol, July 1, 2006; 101(1): 14 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M Gallagher, P. J Fadel, S. A Smith, M. Stromstad, K. Ide, N. H Secher, and P. B Raven The interaction of central command and the exercise pressor reflex in mediating baroreflex resetting during exercise in humans Exp Physiol, January 1, 2006; 91(1): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A Smith, J. H Mitchell, and M. G Garry The mammalian exercise pressor reflex in health and disease Exp Physiol, January 1, 2006; 91(1): 89 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Koba, T. Yoshida, and N. Hayashi Renal sympathetic and circulatory responses to activation of the exercise pressor reflex in rats Exp Physiol, January 1, 2006; 91(1): 111 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Smith, J. H. Mitchell, R. H. Naseem, and M. G. Garry Mechanoreflex Mediates the Exaggerated Exercise Pressor Reflex in Heart Failure Circulation, October 11, 2005; 112(15): 2293 - 2300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J Joyner Found in translation: neural feedback from exercising muscles J. Physiol., September 1, 2005; 567(2): 362 - 363. [Full Text] [PDF]
|
|