Abstract
Autonomic responses to activation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1) has been reported to contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP) responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves' TRPA1 plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24–72 h of femoral artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV); and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia.
Highlights
Peripheral arterial disease (PAD) is atherosclerotic disease with a decrease in blood flow to the arteries of the lower extremities
The purpose of the present study was to determine whether TRPA1 on primary muscle afferent nerves contributes to the enhanced sympathetic responsiveness elicited by femoral artery ligation
The results of this study have shown that that 24 and 72 h of femoral artery occlusion significantly amplifies the protein levels of TRPA1 in lumbar dorsal root ganglion (DRG) of ligated limbs, and that increased expression of TRPA1 selectively appears within DRG neurons that supply C-fiber afferents but not A-fiber afferents
Summary
Peripheral arterial disease (PAD) is atherosclerotic disease with a decrease in blood flow to the arteries of the lower extremities In this disease, the most common symptom is intermittent claudication, which is worsened by exercise activity due to muscle ischemia but subsides at when the metabolic demand of the active muscles is decreased (Rejeski et al, 2008). Namely central command and the exercise pressor reflex, evoke this exercise-induced increase in SNA. The exercise pressor reflex postulates that thin fiber muscle afferent nerves (group III & IV) innervating skeletal muscles are activated by contractioninduced mechanical and metabolic stimuli to elicit a reflex increase in SNA (Mccloskey and Mitchell, 1972; Mitchell et al, 1983; Kaufman and Forster, 1996). The exercise pressor reflex plays a crucial role in evoking the exaggerated BP response to walking in PAD patients (Baccelli et al, 1999)
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