HIF-1α Inhibition Alleviates the Exaggerated Exercise Pressor Reflex in Rats with Peripheral Artery Disease Induced by Femoral Artery Occlusion

Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor mediating adaptive responses to hypoxia and ischemia. Our previous work showed that HIF-1α is increased in muscle sensory nerves of rats with peripheral artery disease (PAD) induced by femoral artery occlusion. The present study was further to examine the role played by HIF-1α in regulating the response of arterial blood pressure (BP) to the activation of muscle afferent nerve during static muscle contraction in rats with femoral artery occlusion. A rat model of femoral artery ligation was used to study PAD in this study. Western blot analysis was employed to examine the protein levels of HIF-1α in the dorsal root ganglion (DRG) tissues. BAY87, a synthesized compound with the characteristics of highly potent and specific suppressive effects on expression and activity of HIF-1α, was given into the arterial blood supply of the ischemic hindlimb muscles before the exercise pressor reflex was evoked by static muscle contraction. First, HIF-1α was increased in the DRG of occluded limbs (optical density: 0.89 ± 0.13 in control versus 1.5 ± 0.05 in occlusion; p < 0.05, n = 6 in each group). Arterial injection of BAY87 (0.2 mg/kg) then inhibited expression of HIF-1α in the DRG of occluded limbs 3 hr following its injection (optical density: 1.02 ± 0.09 in occluded limbs with BAY87 versus 1.06 ± 0.1 in control limbs; p > 0.05, n = 5 in each group). In addition, muscle contraction evoked a greater increase in BP in occluded rats. BAY87 attenuated the enhanced BP response in occluded rats to a greater degree than in control rats. Our data suggest that the inhibition of HIF-1α alleviates the exaggeration of the exercise pressor reflex in rats under ischemic circumstances of the hindlimbs in PAD induced by femoral artery occlusion.