Heart and Vascular Institute, Pennsylvania State College of Medicine, Hershey, Pennsylvania.
Am J Physiol Heart Circ Physiol. 2020 Jul 1;319(1):H171-H182. doi: 10.1152/ajpheart.00257.2020. Epub 2020 Jun 5.
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 blockers into the arterial supply of the triceps surae muscles with and without the femoral artery ligated on the reflex pressor responses to ) static contraction of the triceps surae muscles, ) calcaneal tendon stretch, and ) 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 μg/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. 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.
ASIC1a 在诱发模拟外周动脉疾病大鼠运动升压反射中的作用尚不清楚。这促使我们确定 ASIC1a 是否在外周动脉疾病大鼠去大脑状态下模拟外周动脉疾病时诱发过度运动升压反射中发挥作用。为了模拟外周动脉疾病，我们在实验前 72 小时结扎左侧股动脉。右侧股动脉自由灌注，作为对照。为了验证我们的假设，我们测量了在股动脉结扎和不结扎的情况下，向比目鱼肌动脉供应注射两种 ASIC1a 阻滞剂对）比目鱼肌静态收缩反射性加压反应、）跟腱拉伸和）动脉内注射二质子化磷酸盐（pH 6.0）的影响。我们发现，ASIC1a 阻滞剂 psalmotoxin-1（200ng/kg）和 mambalgin-1（6.5μg/kg）降低了自由灌注后肢诱发的静态收缩加压反应以及二质子化磷酸盐注射引起的峰值加压反应。相比之下，ASIC1a 阻滞剂仅降低了模拟外周动脉疾病的后肢循环中注射二质子化磷酸盐引起的峰值加压反应。这种抑制作用小于从健康后肢测量到的作用。与感兴趣的后肢无关，ASIC1a 阻滞剂对跟腱拉伸引起的加压反应没有影响。我们的结果不支持 ASIC1a 在诱发模拟外周动脉疾病后肢运动升压反射中起作用的假说。ASIC1a 在诱发外周动脉疾病运动升压反射代谢成分中的作用尚不清楚。使用大鼠实验设计，我们发现外周动脉疾病大鼠模型中 ASIC1a 的作用降低。这些结果对外周动脉疾病患者的治疗和改善发病率、生活质量和死亡率具有关键意义。
