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Contribution of nerve growth factor to upregulation of P2X(3) expression in DRG neurons of rats with femoral artery occlusion

Femoral artery occlusion augments the sympathetic nerve and pressor responses to muscle contraction and muscle metabolites injected into the arterial blood supply of the hindlimb muscles in rats. The underlying mechanism by which these reflex responses are enhanced after muscle vascular insufficiency is unclear. Purinergic P2X(3) receptor has been reported to contribute to the metabolic component of the exercise pressor reflex. Thus the purpose of this study was to examine if chronic femoral occlusion would alter the expression of P2X(3) in dorsal root ganglion (DRG) neurons of rats. Also, P2X(3)-mediated sympathetic responsiveness was examined after femoral occlusion. In addition, the role played by nerve growth factor (NGF) in regulating the expression and response of P2X(3) was examined. Western blot analysis showed that 24 h of femoral ligation increased the levels of P2X(3) (optical density: 0.93 +/- 0.07 in control and 1.37 +/- 0.10 after occlusion; P < 0.05 vs. control). The fluorescence immunohistochemistry further demonstrated that the occlusion elevated P2X(3) expression in DRG neurons (percentage of P2X(3)-positive cells: 33 +/- 3% in control and 51 +/- 3% in occlusion; P < 0.05 vs. control). Furthermore, the results showed that responses of renal sympathetic nerve activity and blood pressure to stimulation of P2X were greater in occluded rats than responses in control rats by injection of alpha,beta-methylene ATP into the arterial blood supply of the hindlimb muscle. Finally, infusion of NGF in the hindlimb muscles of healthy rats increased P2X(3) (optical density: 0.98 +/- 0.12 in control and 1.37 +/- 0.16 with NGF; P < 0.05 vs. control). The pressor response to injection of alpha,beta-methylene ATP was increased in the rats with NGF infusion. Likewise, blocking NGF attenuated exaggeration of the reflex response induced by alpha,beta-methylene ATP in occluded rats. The findings of this study suggest that the levels of P2X(3) in primary afferent neurons are upregulated as the blood supply to the hindlimb is deficient under ischemic conditions, leading to augmentation of the muscle reflex. NGF is closely related to increases in P2X(3) receptor expression and response

Keywords : Adenosine Triphosphate,administration & dosage,agonists,analogs & derivatives,analysis,Analysis of Variance,Animals,Arterial Occlusive Diseases,Arteries,blood,Blood Pressure,blood supply,Blotting,Western,complications,Constriction,Pathologic,Disease Models,Animal,drug effects,etiology,Femoral Artery,Fluorescent Antibody Technique,Ganglia,Spinal,Growth,Heart,Heart Rate,Hindlimb,Immunohistochemistry,Infusions,Parenteral,Injections,Intra-Arterial,innervation,Ischemia,Kidney,Ligation,Male,metabolism,Muscle Contraction,Muscle,Skeletal,Nerve Growth Factor,Neurons,physiopathology,Pressure,Purinergic P2X Receptor Agonists,Rats,Rats,Sprague-Dawley,Receptors,Purinergic P2X3,Reflex,Reflex,Abnormal,Sympathetic Nervous System,Time Factors,Up-Regulation,, Nerve,Growth,Factor, harley street mri

Date of Publication : 2011 Sep

Authors : Liu J;Li JD;Lu J;Xing J;Li J;

Organisation : Penn State Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA

Journal of Publication : Am J Physiol Heart Circ Physiol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21642505

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