Xing Jihong, Lu Jian, Li Jianhua
Heart & Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, PA, United States.
Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, China.
Front Physiol. 2018 Oct 15;9:1461. doi: 10.3389/fphys.2018.01461. eCollection 2018.
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.
在股动脉闭塞的大鼠中,运动升压反射激活期间交感神经活动和动脉血压的反应增强。本研究探讨了促炎细胞因子肿瘤坏死因子-α(TNF-α)在调节股动脉闭塞72小时后肌肉代谢受体刺激和静态肌肉收缩诱导的交感反应增强中所起的作用。我们首先观察到,股动脉闭塞的后肢背根神经节(DRG)中TNF-α水平和1型TNF-α受体(TNFR1)的蛋白表达增加。注意,在C纤维传入神经的DRG神经元内观察到了TNF-α。将辣椒素(TRPV1激动剂)和异硫氰酸烯丙酯(TRPA1激动剂)注入后肢的动脉血液供应中,以刺激代谢敏感的细纤维肌肉传入神经。在对照大鼠和股动脉闭塞大鼠中进一步研究了这些注射对交感和升压反应的影响。由于之前已将TNF-α合成抑制剂己酮可可碱(PTX)注入股动脉闭塞的后肢,辣椒素和异硫氰酸烯丙酯诱导的交感和升压反应减弱。在闭塞大鼠中,PTX还减弱了肌肉收缩而非被动肌腱拉伸诱导的血压反应的增强。总体而言,结果表明,当外周动脉疾病中后肢肌肉缺血时,TNF-α通过运动升压反射的代谢成分在调节过度的交感神经活动中发挥作用。