Neutralization of NGF Attenuates Augmented Sympathetic Nerve Responses to Activation of Chemically Sensitive Muscle Afferents in Rats with Femoral Artery Occlusion

Abstract

Arterial blood pressure and heart rate responses to static contraction of the hindlimb muscles are greater in rats whose femoral artery is previously ligated than in control rats. Also, the prior findings demonstrate that nerve growth factor (NGF) is amplified in dorsal root ganglion (DRG) neurons of occluded rats. NGF has been reported to sensitize responsiveness to mechanical and chemical stimuli via thin fiber afferent nerves. Thus, the present study was first to examine the role for NGF in engagement of the augmented sympathetic and pressor responses to muscle contraction and passive tendon stretch after 24 hrs of femoral artery ligation. The data showed that femoral occlusion‐augmented blood pressure response to contraction was significantly attenuated by the prior administration of NGF antibody into the hindlimb muscles. The effects of NGF neutralization were not seen as the sympathetic and pressor responses were evoked by stimulation of muscle mechanically sensitive afferent nerves with muscle stretch in occluded rats. In addition, chemically sensitive afferent nerves were stimulated by lactic acid injected into the arterial blood supply of the hindlimb muscles after the prior injection of NGF antibody, demonstrating that the reflex responses to lactic acid were significantly attenuated. Moreover, immunohistochemistry was employed to examine the number of DRG neurons that project C‐fiber and A‐fiber. The data showed that distribution of DRG neurons with thin fiber phenotypes was not notably altered as NGF was infused into the hindlimb muscles. However, NGF increased expression of acid sensing ion channel subtype 3 in DRG neurons with thin C‐fiber, but not A‐fiber. Overall, these data suggest that NGF increased in sensory nerves of occluded rats is likely engaged in augmented reflex sympathetic and blood pressure responses evoked by stimulation of chemically, but not mechanically sensitive muscle afferent nerves.