TY - JOUR
T1 - The capsaicin-sensetive afferent neuron in skeletal muscle is abnormal in heart failure
AU - Smith, Scott A.
AU - Williams, Maurice A.
AU - Mitchell, Jere H.
AU - Mammen, Pradeep P.A.
AU - Garry, Mary G.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4/26
Y1 - 2005/4/26
N2 - 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 TV 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 TV 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.
AB - 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 TV 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 TV 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.
KW - Blood pressure
KW - Cardiomyopathy
KW - Exercise
KW - Heart failure
KW - Reflex
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U2 - 10.1161/01.CIR.0000162473.10951.0A
DO - 10.1161/01.CIR.0000162473.10951.0A
M3 - Article
C2 - 15851614
AN - SCOPUS:17744390876
SN - 0009-7322
VL - 111
SP - 2056
EP - 2065
JO - Circulation
JF - Circulation
IS - 16
ER -