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热处理通过降低 P2X 受体途径的活性来改善股动脉闭塞大鼠的过度运动升压反射。

Heat treatment improves the exaggerated exercise pressor reflex in rats with femoral artery occlusion via a reduction in the activity of the P2X receptor pathway.

机构信息

Heart & Vascular Institute, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA.

出版信息

J Physiol. 2020 Apr;598(8):1491-1503. doi: 10.1113/JP279230. Epub 2020 Mar 23.

Abstract

KEY POINTS

During exercise, the blood pressure (BP) response is exaggerated in peripheral artery disease (PAD). We examined whether heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in PAD rats. With HT (increase in basal muscle temperature of ∼1.5°C for 30 min, twice daily for three continuous days), the amplified BP response to muscle contraction is alleviated in PAD. We demonstrated that HT attenuates the enhancement of the BP response induced by stimulation of P2X in muscle afferent nerves of PAD rats. HT also attenuates the upregulation of the P2X and the increase in P2X currents in the muscle afferent neurons of PAD rats. Previous heat exposure plays a beneficial role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction in the activity of the P2X receptor pathway is probably a part of the mechanism mediating this improvement.

ABSTRACT

The current study was performed to examine if heat treatment (HT) has beneficial effects on the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD). We further determined if the temperature-sensitive P2X receptor is involved in the effects of HT. The pressor response to static muscle contraction and α,β-methylene ATP (αβ-me ATP, a P2X agonist) was examined. Western blot analysis was used to determine the protein levels of P2X in the dorsal root ganglion (DRG), and the whole cell patch clamp was used to examine the amplitude of P2X currents in the DRG neurons. The basal muscle temperature (T ) was lower in PAD rats than in control rats. T was increased by ∼1.5°C and this increase was maintained for 30 min. This HT protocol was performed tweice daily for three continuous days. A greater blood pressure (BP) response to contraction was observed in PAD rats. HT attenuated the amplification of the BP response in PAD rats. HT also attenuated the enhancement of the BP response induced by the arterial injection of αβ-me ATP in PAD rats. In addition, HT attenuated the upregulation of the P2X and increased P2X currents in the DRG neurons of PAD rats. In conclusion, previous heat exposure plays an inhibitory role in modifying the exaggeration of the exercise pressor reflex in PAD and a reduction of the activity of the P2X receptor pathway is probably a part of mechanisms leading to the beneficial effects of HT.

摘要

要点

在周围动脉疾病(PAD)患者中,运动时血压(BP)反应会被夸大。我们研究了热疗(HT)是否对 PAD 大鼠过度的运动加压反射有有益的影响。通过 HT(基础肌肉温度升高约 1.5°C,持续 3 天,每天 2 次),可以缓解 PAD 大鼠肌肉收缩引起的血压反应过度增强。我们发现 HT 可减弱 PAD 大鼠肌肉传入神经中 P2X 刺激引起的 BP 反应增强。HT 还可减弱 PAD 大鼠肌肉传入神经元中 P2X 的上调和 P2X 电流的增加。先前的热暴露对改善 PAD 运动加压反射的过度增强起到了有益的作用,而 P2X 受体途径活性的降低可能是介导这种改善的机制的一部分。

摘要

本研究旨在探讨热疗(HT)是否对周围动脉疾病(PAD)大鼠过度的运动加压反射有有益的影响。我们还进一步确定温度敏感型 P2X 受体是否参与了 HT 的作用。检测了静态肌肉收缩和 α,β-亚甲基 ATP(αβ-meATP,P2X 激动剂)引起的加压反应。Western blot 分析用于确定背根神经节(DRG)中 P2X 的蛋白水平,全细胞膜片钳用于检测 DRG 神经元中 P2X 电流的幅度。PAD 大鼠的基础肌肉温度(T)低于对照组大鼠。T 升高约 1.5°C,维持 30 分钟。此 HT 方案每天进行两次,持续 3 天。PAD 大鼠的收缩引起的血压(BP)反应更大。HT 减弱了 PAD 大鼠的 BP 反应增强。HT 还减弱了 PAD 大鼠动脉内注射 αβ-meATP 引起的 BP 反应增强。此外,HT 减弱了 PAD 大鼠 DRG 神经元中 P2X 的上调和增加的 P2X 电流。总之,先前的热暴露在抑制 PAD 运动加压反射的过度增强方面发挥了抑制作用,而 P2X 受体途径活性的降低可能是 HT 有益作用的部分机制。

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