Heart and Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
Physiol Rep. 2021 Jan;8(24):e14676. doi: 10.14814/phy2.14676.
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.
缺氧诱导因子 1α（HIF-1α）是一种转录因子，介导对缺氧和缺血的适应性反应。我们之前的工作表明，在由股动脉闭塞引起的周围动脉疾病（PAD）大鼠的肌肉感觉神经中，HIF-1α增加。本研究进一步研究了 HIF-1α在调节股动脉闭塞大鼠肌肉传入神经激活时动脉血压（BP）对静态肌肉收缩反应中的作用。在这项研究中，使用大鼠股动脉结扎模型来研究 PAD。采用 Western blot 分析检测背根神经节（DRG）组织中 HIF-1α的蛋白水平。BAY87 是一种合成化合物，具有高度有效和特异抑制 HIF-1α表达和活性的特性，在通过静态肌肉收缩引起运动加压反射之前，将其注入缺血性后肢肌肉的动脉血液供应中。首先，在闭塞肢体的 DRG 中增加了 HIF-1α（对照为 0.89±0.13，闭塞为 1.5±0.05；p<0.05，每组 6 只）。股动脉注射 BAY87（0.2mg/kg）可抑制 3 小时后闭塞肢体 DRG 中 HIF-1α的表达（BAY87 闭塞肢体的光密度为 1.02±0.09，对照肢体为 1.06±0.1；p>0.05，每组 5 只）。此外，肌肉收缩引起闭塞大鼠 BP 更大幅度的增加。BAY87 减轻了闭塞大鼠增强的 BP 反应，其程度大于对照大鼠。我们的数据表明，在股动脉闭塞引起的 PAD 大鼠后肢缺血情况下，抑制 HIF-1α可减轻运动加压反射的夸大。
