Role of TNF‐α in Regulating Augmented Exercise Pressor Reflex Induced by Femoral Artery Occlusion

Using a rat model, our prior study has demonstrated that TNF‐α contributes to augmented sympathetic nerve and blood pressure responses evoked by activation of metabolic receptors (i.e., TRPV1 and TRPA1) on thin fiber muscle afferent nerves when the blood flow to hindlimb is occluded for 72 hrs. The present study was to examine the role played by TNF‐α in augmented sympathetic responsiveness during the exercise pressor reflex following 72 hrs of femoral artery occlusion. The exercise pressor reflex was evoked by static muscle contraction and passive tendon stretch in rats. Our results show that femoral occlusion significantly enhanced blood pressure response to muscle contraction and stretch ( P <0.05) as compared with controls. TNF‐α synthesis suppressor pentoxifylline (PTX) administered previously into the hindlimb muscles significantly attenuates amplified blood pressure response induced by muscle contraction in occluded rats (MAP: 19±1 mmHg with PTX and 26±2 mmHg without PTX, n=6 in each group; P <0.05 vs. PTX group). However, PTX failed to significantly alter amplified pressor response induced by muscle stretch in occluded rats (MAP: 21±2 mmHg with PTX and 23±2 mmHg without PTX, n=5 in each group; P >0.05 vs. PTX group). Overall, our data suggest that TNF‐α plays a role in modulating augmented sympathetic responsiveness via the metabolic component of the exercise pressor reflex when arterial blood supply to the hindlimb is deficient under ischemic conditions as observed in peripheral artery disease. This study was supported by NIH P01 HL096570