ASIC1a does not play a role in evoking the metabolic component of the exercise pressor reflex in a rat model of peripheral artery disease
ASIC1a does not play a role in evoking the metabolic component of the exercise pressor reflex in a rat model of peripheral artery disease
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DOI：
10.1152/ajpheart.00257.2020
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发表时间：
2020-07-01
影响因子：
4.8
通讯作者：
Kaufman, Marc P.
中科院分区：
文献类型：
--
作者：
Ducrocq, Guillaume P.;Kim, Joyce S.;Kaufman, Marc P.
ASIC1a在模拟外周动脉疾病大鼠中引发运动加压反射的作用尚不清楚。这促使我们确定ASIC1a是否在模拟外周动脉疾病的失脑大鼠中引起夸大的运动压力反射中起作用。为了模拟外周动脉病变，我们在实验前72小时结扎左股动脉。右股动脉自由灌注并作为对照。为了验证我们的假设，我们测量了将两种ASIC1a阻断剂注射到有股动脉和没有股动脉结扎的三头肌表面肌肉的动脉供应中，对反射加压反应的影响：1)三头肌表面肌肉的静态收缩，2)跟腱拉伸，以及3)动脉内注射双质子化磷酸盐（pH 6.0）。我们发现ASIC1a阻滞剂psalmotoxin-1 （200 ng/kg）和mambalin -1 （6.5 mu g/kg）降低了静态收缩时的压力反应，以及在自由灌注的后肢诱发双质子化磷酸盐注射时的压力反应峰值。相比之下，ASIC1a阻滞剂仅降低了模拟外周动脉疾病后肢循环中注射双质子化磷酸盐引起的峰值压力反应。这种抑制作用小于健康后肢的抑制作用。独立于后肢，ASIC1a阻滞剂对肌腱拉伸的加压反应没有影响。我们的结果不支持ASIC1a在引起模拟外周动脉疾病的后肢运动压力反射中起作用的假设。ASIC1a在外周动脉疾病中引发运动加压反射代谢成分中的作用尚不清楚。采用大鼠内实验设计。我们发现ASIC1a在外周动脉疾病大鼠模型中的作用有所下降。这些结果对于帮助寻找更好的治疗方法，改善外周动脉疾病患者的发病率、生活质量和死亡率具有重要意义。
The role of the ASIC1a in evoking the exercise pressor reflex in rats with simulated peripheral artery disease is unknown. This prompted us to determine whether ASIC1a plays a role in evoking the exaggerated exercise pressor reflex in decerebrated rats with simulated peripheral artery disease. To simulate peripheral artery disease, we ligated the left femoral artery 72 h before the experiment. The right femoral artery was freely perfused and used as a control. To test our hypothesis, we measured the effect of injecting two ASIC1a blockeis into the arterial supply of the triceps surae muscles with and without the femoral artery ligated on the reflex pressor responses to 1) static contraction of the triceps surae muscles, 2) calcaneal tendon stretch, and 3) intra-arterial injection of diprotonated phosphate (pH 6.0). We found that the ASIC1a blockers psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 mu g/kg) decreased the pressor responses to static contraction as well as the peak pressor responses to injection of diprotonated phosphate when these responses were evoked from the freely perfused hindlimb. In contrast, ASIC1a blockers only decreased the peak pressor responses evoked by injection of diprotonated phosphate in the hindlimb circulation with simulated peripheral artery disease. This inhibitory effect was less than the one measured from the healthy hindlimb. Independently of the hindlimb of interest, ASIC1a blockers had no effect on the pressor responses to tendon stretch. Our results do not support the hypothesis that ASIC1a play a role in evoking the exercise pressor reflex arising from a hindlimb with simulated peripheral artery disease.NEW & NOTEWORTHY The role of ASIC1a in evoking the metabolic component of the exercise pressor reflex in peripheral artery disease is unknown. Using a within-rat experimental design. we found that the contribution of ASIC1a decreased in a rat model of peripheral artery disease. These results have key implications to help finding better treatments and improve morbidity, quality of life, and mortality in patients with peripheral artery disease.