Muscle metabolic by-products stimulate thin fiber muscle afferent nerves and evoke reflex increases in blood pressure and sympathetic nerve activity. Previous studies reported that chemically sensitive transient receptor potential vanilloid type 1 (TRPV1) channels present on sensory muscle afferent neurons have an important impact on sympathetically mediated cardiovascular responses. The reflex mediated reduction in blood flow to skeletal muscle leads to limited exercise capacity in patients with peripheral arterial occlusive disease. Thus, in this report we tested the hypothesis that enhanced TRPV1 receptor's expression and its responsiveness in primary afferent neurons innervating muscles initiate exaggerated reflex sympathetic responses after vascular insufficiency to the muscle. Muscle vascular insufficiency was induced by the femoral artery ligation in rats for 24 hrs. Our data show that: 1) the ligation surgery leads to upregulation of TRPV1 expression in the dorsal root ganglion (DRG); 2) the magnitude of the DRG neuron TRPV1 response induced by capsaicin is greater in vascular insufficiency (4.0 ± 0.31 nA, P < 0.05 vs. sham-control) than that in sham-control (2.9 ± 0.23 nA); and 3) renal sympathetic nerve activity and mean arterial pressure responses to capsaicin (0.5 µg/kg body weight) are also enhanced by vascular insufficiency (54 ± 11%, 9 ± 2 mmHg in sham-controls vs. 98 ± 13%, 33 ± 5 mmHg after vascular insufficiency, P < 0.05). In conclusion, sympathetic nerve responses to activation of metabolite-sensitive TRPV1 receptors are augmented in rats with the femoral artery occlusion compared with sham-control animals, due to alterations in TRPV1 receptor's expression and its responsiveness in sensory neurons.