Contribution of nerve growth factor to upregulation of P2X3 expression in DRG neurons of rats with femoral artery occlusion

Jiahao Liu, Jialiu David Li, Jian Lu, Jihong Xing, Jianhua Li

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Femoral artery occlusion augments the sympathetic nerve and pressorresponses to muscle contraction and muscle metabolites injected intothe arterial blood supply of the hindlimb muscles in rats. The underlyingmechanism by which these reflex responses are enhanced aftermuscle vascular insufficiency is unclear. Purinergic P2X3 receptor hasbeen reported to contribute to the metabolic component of the exercisepressor reflex. Thus the purpose of this study was to examine ifchronic femoral occlusion would alter the expression of P2X3 indorsal root ganglion (DRG) neurons of rats. Also, P2X3-mediatedsympathetic responsiveness was examined after femoral occlusion. Inaddition, the role played by nerve growth factor (NGF) in regulatingthe expression and response of P2X3 was examined. Western blotanalysis showed that 24 h of femoral ligation increased the levels ofP2X3 (optical density: 0.93 ± 0.07 in control and 1.37 ± 0.10 afterocclusion; P < 0.05 vs. control). The fluorescence immunohistochemistryfurther demonstrated that the occlusion elevated P2X3 expressionin DRG neurons (percentage of P2X3-positive cells: 33 ± 3% incontrol and 51 ± 3% in occlusion; P < 0.05 vs. control). Furthermore,the results showed that responses of renal sympathetic nerve activityand blood pressure to stimulation of P2X were greater in occluded ratsthan responses in control rats by injection of α,β-methylene ATP intothe arterial blood supply of the hindlimb muscle. Finally, infusion ofNGF in the hindlimb muscles of healthy rats increased P2X3 (opticaldensity: 0.98 ± 0.12 in control and 1.37 ± 0.16 with NGF; P < 0.05vs. control). The pressor response to injection of α,β-methylene ATPwas increased in the rats with NGF infusion. Likewise, blocking NGFattenuated exaggeration of the reflex response induced by α,β-methyleneATP in occluded rats. The findings of this study suggest that thelevels of P2X3 in primary afferent neurons are upregulated as theblood supply to the hindlimb is deficient under ischemic conditions,leading to augmentation of the muscle reflex. NGF is closely relatedto increases in P2X3 receptor expression and response.

Original languageEnglish (US)
Pages (from-to)H1070-H1079
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number3
DOIs
StatePublished - Sep 1 2011

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Diagnosis-Related Groups
Nerve Growth Factor
Femoral Artery
Up-Regulation
Hindlimb
Neurons
Reflex
Purinergic P2X3 Receptors
Muscles
Thigh
Afferent Neurons
Injections
Muscle Contraction
Ganglia
Ligation
Blood Vessels
Adenosine Triphosphate
Fluorescence
Blood Pressure
Kidney

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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title = "Contribution of nerve growth factor to upregulation of P2X3 expression in DRG neurons of rats with femoral artery occlusion",
abstract = "Femoral artery occlusion augments the sympathetic nerve and pressorresponses to muscle contraction and muscle metabolites injected intothe arterial blood supply of the hindlimb muscles in rats. The underlyingmechanism by which these reflex responses are enhanced aftermuscle vascular insufficiency is unclear. Purinergic P2X3 receptor hasbeen reported to contribute to the metabolic component of the exercisepressor reflex. Thus the purpose of this study was to examine ifchronic femoral occlusion would alter the expression of P2X3 indorsal root ganglion (DRG) neurons of rats. Also, P2X3-mediatedsympathetic responsiveness was examined after femoral occlusion. Inaddition, the role played by nerve growth factor (NGF) in regulatingthe expression and response of P2X3 was examined. Western blotanalysis showed that 24 h of femoral ligation increased the levels ofP2X3 (optical density: 0.93 ± 0.07 in control and 1.37 ± 0.10 afterocclusion; P < 0.05 vs. control). The fluorescence immunohistochemistryfurther demonstrated that the occlusion elevated P2X3 expressionin DRG neurons (percentage of P2X3-positive cells: 33 ± 3{\%} incontrol and 51 ± 3{\%} in occlusion; P < 0.05 vs. control). Furthermore,the results showed that responses of renal sympathetic nerve activityand blood pressure to stimulation of P2X were greater in occluded ratsthan responses in control rats by injection of α,β-methylene ATP intothe arterial blood supply of the hindlimb muscle. Finally, infusion ofNGF in the hindlimb muscles of healthy rats increased P2X3 (opticaldensity: 0.98 ± 0.12 in control and 1.37 ± 0.16 with NGF; P < 0.05vs. control). The pressor response to injection of α,β-methylene ATPwas increased in the rats with NGF infusion. Likewise, blocking NGFattenuated exaggeration of the reflex response induced by α,β-methyleneATP in occluded rats. The findings of this study suggest that thelevels of P2X3 in primary afferent neurons are upregulated as theblood supply to the hindlimb is deficient under ischemic conditions,leading to augmentation of the muscle reflex. NGF is closely relatedto increases in P2X3 receptor expression and response.",
author = "Jiahao Liu and Li, {Jialiu David} and Jian Lu and Jihong Xing and Jianhua Li",
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Contribution of nerve growth factor to upregulation of P2X3 expression in DRG neurons of rats with femoral artery occlusion. / Liu, Jiahao; Li, Jialiu David; Lu, Jian; Xing, Jihong; Li, Jianhua.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 3, 01.09.2011, p. H1070-H1079.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Contribution of nerve growth factor to upregulation of P2X3 expression in DRG neurons of rats with femoral artery occlusion

AU - Liu, Jiahao

AU - Li, Jialiu David

AU - Lu, Jian

AU - Xing, Jihong

AU - Li, Jianhua

PY - 2011/9/1

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N2 - Femoral artery occlusion augments the sympathetic nerve and pressorresponses to muscle contraction and muscle metabolites injected intothe arterial blood supply of the hindlimb muscles in rats. The underlyingmechanism by which these reflex responses are enhanced aftermuscle vascular insufficiency is unclear. Purinergic P2X3 receptor hasbeen reported to contribute to the metabolic component of the exercisepressor reflex. Thus the purpose of this study was to examine ifchronic femoral occlusion would alter the expression of P2X3 indorsal root ganglion (DRG) neurons of rats. Also, P2X3-mediatedsympathetic responsiveness was examined after femoral occlusion. Inaddition, the role played by nerve growth factor (NGF) in regulatingthe expression and response of P2X3 was examined. Western blotanalysis showed that 24 h of femoral ligation increased the levels ofP2X3 (optical density: 0.93 ± 0.07 in control and 1.37 ± 0.10 afterocclusion; P < 0.05 vs. control). The fluorescence immunohistochemistryfurther demonstrated that the occlusion elevated P2X3 expressionin DRG neurons (percentage of P2X3-positive cells: 33 ± 3% incontrol and 51 ± 3% in occlusion; P < 0.05 vs. control). Furthermore,the results showed that responses of renal sympathetic nerve activityand blood pressure to stimulation of P2X were greater in occluded ratsthan responses in control rats by injection of α,β-methylene ATP intothe arterial blood supply of the hindlimb muscle. Finally, infusion ofNGF in the hindlimb muscles of healthy rats increased P2X3 (opticaldensity: 0.98 ± 0.12 in control and 1.37 ± 0.16 with NGF; P < 0.05vs. control). The pressor response to injection of α,β-methylene ATPwas increased in the rats with NGF infusion. Likewise, blocking NGFattenuated exaggeration of the reflex response induced by α,β-methyleneATP in occluded rats. The findings of this study suggest that thelevels of P2X3 in primary afferent neurons are upregulated as theblood supply to the hindlimb is deficient under ischemic conditions,leading to augmentation of the muscle reflex. NGF is closely relatedto increases in P2X3 receptor expression and response.

AB - Femoral artery occlusion augments the sympathetic nerve and pressorresponses to muscle contraction and muscle metabolites injected intothe arterial blood supply of the hindlimb muscles in rats. The underlyingmechanism by which these reflex responses are enhanced aftermuscle vascular insufficiency is unclear. Purinergic P2X3 receptor hasbeen reported to contribute to the metabolic component of the exercisepressor reflex. Thus the purpose of this study was to examine ifchronic femoral occlusion would alter the expression of P2X3 indorsal root ganglion (DRG) neurons of rats. Also, P2X3-mediatedsympathetic responsiveness was examined after femoral occlusion. Inaddition, the role played by nerve growth factor (NGF) in regulatingthe expression and response of P2X3 was examined. Western blotanalysis showed that 24 h of femoral ligation increased the levels ofP2X3 (optical density: 0.93 ± 0.07 in control and 1.37 ± 0.10 afterocclusion; P < 0.05 vs. control). The fluorescence immunohistochemistryfurther demonstrated that the occlusion elevated P2X3 expressionin DRG neurons (percentage of P2X3-positive cells: 33 ± 3% incontrol and 51 ± 3% in occlusion; P < 0.05 vs. control). Furthermore,the results showed that responses of renal sympathetic nerve activityand blood pressure to stimulation of P2X were greater in occluded ratsthan responses in control rats by injection of α,β-methylene ATP intothe arterial blood supply of the hindlimb muscle. Finally, infusion ofNGF in the hindlimb muscles of healthy rats increased P2X3 (opticaldensity: 0.98 ± 0.12 in control and 1.37 ± 0.16 with NGF; P < 0.05vs. control). The pressor response to injection of α,β-methylene ATPwas increased in the rats with NGF infusion. Likewise, blocking NGFattenuated exaggeration of the reflex response induced by α,β-methyleneATP in occluded rats. The findings of this study suggest that thelevels of P2X3 in primary afferent neurons are upregulated as theblood supply to the hindlimb is deficient under ischemic conditions,leading to augmentation of the muscle reflex. NGF is closely relatedto increases in P2X3 receptor expression and response.

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