Role of TNF-α in Regulating the Exercise Pressor Reflex in Rats With Femoral Artery Occlusion.

Jihong Xing,Jian Lu,Jianhua Li

doi:10.3389/fphys.2018.01461

Abstract

Responses of sympathetic nerve activity and arterial blood pressure are augmented during activation of the exercise pressor reflex in rats with femoral artery occlusion. The present study examined the role played by proinflammatory tumor necrosis factor-α (TNF-α) in regulating augmented sympathetic responsiveness induced by stimulation of muscle metabolic receptors and static muscle contraction following 72 h of femoral artery occlusion. We first observed that the levels of TNF-α and protein expression of TNF-α receptor type 1 (TNFR1) were increased in the dorsal root ganglion (DRG) of hindlimbs with femoral artery occlusion. Note that TNF-α was observed within DRG neurons of C-fiber afferent nerves. Capsaicin (TRPV1 agonist) and AITC (TRPA1 agonist) were injected into arterial blood supply of the hindlimbs to stimulate metabolically sensitive thin-fiber muscle afferents. The effects of these injections on the sympathetic and pressor responses were further examined in control rats and rats with femoral artery occlusion. As TNF-α synthesis suppressor pentoxifylline (PTX) was previously administered into the hindlimb with femoral artery occlusion, sympathetic, and pressor responses induced by capsaicin and AITC were attenuated. In occluded rats, PTX also attenuated the exaggeration of blood pressure response induced by muscle contraction, but not by passive tendon stretch. Overall, the results suggest that TNF-α plays a role in modulating exaggerated sympathetic nervous activity via the metabolic component of the exercise pressor reflex when the hindlimb muscles are ischemic in peripheral arterial disease.

Highlights

Exercise activity increases sympathetic nervous activity (SNA) and decreases parasympathetic activity and thereby amplifies blood pressure (BP) and heart rate (HR), myocardial contractility and peripheral vasoconstriction (Mitchell et al, 1983)
Seventy-two hours of femoral artery occlusion significantly increased the levels of tumor necrosis factorα (TNF-α) in the dorsal root ganglion (DRG) tissues of ischemic limbs as compare with control limbs (n = 6 in each group)
We examined if TNF-α exists within DRG neurons projecting C- and/or A-fiber afferents

Summary

Introduction

Exercise activity increases sympathetic nervous activity (SNA) and decreases parasympathetic activity and thereby amplifies blood pressure (BP) and heart rate (HR), myocardial contractility and peripheral vasoconstriction (Mitchell et al, 1983). A mechanism termed the “Exercise Pressor Reflex” contributes to sympathetic engagement during exercise (McCloskey and Mitchell, 1972; Mitchell et al, 1983). This autonomic reflex is evoked when thin fiber afferents arising from contracting skeletal muscle are activated (Kaufman and Forster, 1996). Intra-arterial injection of chemicals (i.e., capsaicin and AITC) stimulating metabosensitive transient receptor potential vanilloid receptor 1(TRPV1) and transient receptor potential ankyrin 1 (TRPA1) in muscle afferent nerves increases reflex sympathetic and BP responses (Xing et al, 2009, 2015). In the current study, we stimulated TRPV1 and TRPA1 and examined their effects on SNA and BP responses

Methods

Results

Discussion

Conclusion