Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure

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

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2293-2300
Number of pages8
JournalCirculation
Volume112
Issue number15
DOIs
StatePublished - Oct 11 2005

Fingerprint

Reflex
Heart Failure
Arterial Pressure
Heart Rate
Hindlimb
Afferent Neurons
Muscles
Capsaicin
Gadolinium
Muscle Contraction
Sprague Dawley Rats
Control Groups
Population

Keywords

  • Blood pressure
  • Cardiomyopathy
  • Exercise
  • Heart failure
  • Nervous system, autonomic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure. / Smith, Scott A.; Mitchell, Jere H.; Naseem, R. Haris; Garry, Mary G.

In: Circulation, Vol. 112, No. 15, 11.10.2005, p. 2293-2300.

Research output: Contribution to journalArticle

Smith, Scott A. ; Mitchell, Jere H. ; Naseem, R. Haris ; Garry, Mary G. / Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure. In: Circulation. 2005 ; Vol. 112, No. 15. pp. 2293-2300.
@article{dd3528593a98400fa72aa7ad7950c0ca,
title = "Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure",
abstract = "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.",
keywords = "Blood pressure, Cardiomyopathy, Exercise, Heart failure, Nervous system, autonomic",
author = "Smith, {Scott A.} and Mitchell, {Jere H.} and Naseem, {R. Haris} and Garry, {Mary G.}",
year = "2005",
month = "10",
day = "11",
doi = "10.1161/CIRCULATIONAHA.105.566745",
language = "English (US)",
volume = "112",
pages = "2293--2300",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

TY - JOUR

T1 - Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure

AU - Smith, Scott A.

AU - Mitchell, Jere H.

AU - Naseem, R. Haris

AU - Garry, Mary G.

PY - 2005/10/11

Y1 - 2005/10/11

N2 - 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.

AB - 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.

KW - Blood pressure

KW - Cardiomyopathy

KW - Exercise

KW - Heart failure

KW - Nervous system, autonomic

UR - http://www.scopus.com/inward/record.url?scp=26844523679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26844523679&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.105.566745

DO - 10.1161/CIRCULATIONAHA.105.566745

M3 - Article

C2 - 16216976

AN - SCOPUS:26844523679

VL - 112

SP - 2293

EP - 2300

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 15

ER -