Role for NGF in augmented sympathetic nerve response to activation of mechanically and metabolically sensitive muscle afferents in rats with femoral artery occlusion
Role for NGF in augmented sympathetic nerve response to activation of mechanically and metabolically sensitive muscle afferents in rats with femoral artery occlusion
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DOI：
10.1152/japplphysiol.00617.2012
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发表时间：
2012-10-01
影响因子：
3.3
通讯作者：
Li, Jianhua
中科院分区：
文献类型：
--
作者：
Lu, Jian;Xing, Jihong;Li, Jianhua
先前结扎股动脉的大鼠的动脉血压和心率对后肢肌肉静态收缩的反应比对照组大。此外，先前的研究结果表明，神经生长因子（NGF）在封闭大鼠的感觉神经元-背根神经节（DRG）神经元中增加。然而，内源性NGF在股动脉结扎后静态收缩过程中对机械和/或代谢敏感肌肉传入神经的刺激增强交感神经和加压反应中的作用尚未明确确定。在本研究中，通过肌肉收缩、被动肌腱拉伸和动脉向后肢肌肉注射乳酸来激活传入神经和传入神经中的任何一个。数据显示，事先将NGF抗体（NGF- ab）注入后肢肌肉后，股骨闭塞-血压升高对收缩的反应显著减弱。通过拉伸肌腱刺激机械敏感肌传入神经引起交感神经和压力反应时，未观察到NGF中和的作用。此外，在先前的NGF-Ab后，将乳酸注射到后肢肌肉的动脉血供中刺激化学敏感肌传入神经，表明反射肌对乳酸的反应明显减弱。本研究结果进一步表明，NGF-Ab可减弱闭塞大鼠DRG酸敏离子通道亚型3 （ASIC3）的增加。免疫组化法检测c纤维和a纤维DRG神经元数量。结果表明，后肢肌肉注入NGF后，不同细纤维表型的DRG神经元分布无明显改变。然而，NGF增加了c -纤维DRG神经元中ASIC3的表达，而没有增加a -纤维。综上所述，这些数据表明：1)NGF在闭塞大鼠的感觉神经中被放大，并有助于化学刺激而非机械刺激敏感肌肉传入神经引起的反射交感神经和血压反应的增强；2)NGF可能通过增强DRG神经元c纤维中ASIC3的表达来调节肌肉代谢反射。
Arterial blood pressure and heart rate responses to static contraction of the hindlimb muscles are greater in rats whose femoral arteries were previously ligated than in control rats. Also, the prior findings demonstrate that nerve growth factor (NGF) is increased in sensory neurons-dorsal root ganglion (DRG) neurons of occluded rats. However, the role for endogenous NGF in engagement of the augmented sympathetic and pressor responses to stimulation of mechanically and/or metabolically sensitive muscle afferent nerves during static contraction after femoral artery ligation has not been specifically determined. In the present study, both afferent nerves and either of them were activated by muscle contraction, passive tendon stretch, and arterial injection of lactic acid into the hindlimb muscles. Data showed that femoral occlusion-augmented blood pressure response to contraction was significantly attenuated by a prior administration of the NGF antibody (NGF-Ab) into the hindlimb muscles. The effects of NGF neutralization were not seen when the sympathetic nerve and pressor responses were evoked by stimulation of mechanically sensitive muscle afferent nerves with tendon stretch in occluded rats. In addition, chemically sensitive muscle afferent nerves were stimulated by lactic acid injected into arterial blood supply of the hindlimb muscles after the prior NGF-Ab, demonstrating that the reflex muscle responses to lactic acid were significantly attenuated. The results of this study further showed that NGF-Ab attenuated an increase in acid-sensing ion channel subtype 3 (ASIC3) of DRG in occluded rats. Moreover, immunohistochemistry was employed to examine the number of C-fiber and A-fiber DRG neurons. The data showed that distribution of DRG neurons with different thin fiber phenotypes was not notably altered when NGF was infused into the hindlimb muscles. However, NGF increased expression of ASIC3 in DRG neurons with C-fiber but not A-fiber. Overall, these data suggest that 1) NGF is amplified in sensory nerves of occluded rats and contributes to augmented reflex sympathetic and blood pressure responses evoked by stimulation of chemically, but not mechanically, sensitive muscle afferent nerves and 2) NGF likely plays a role in modulating the muscle metaboreflex via enhancement of ASIC3 expression in C-fiber of DRG neurons.