Thromboxane A2 receptors mediate chronic mechanoreflex sensitization in a rat model of simulated peripheral artery disease.
Thromboxane A2 receptors mediate chronic mechanoreflex sensitization in a rat model of simulated peripheral artery disease.
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在模拟外周动脉疾病的大鼠模型中，血栓素 A2 受体介导慢性机械感受反射敏化。
DOI：
10.1152/ajpheart.00255.2020
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Copp,StevenW
中科院分区：
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作者：
Rollins,KorynneS;Butenas,AlecLE;Felice,KennedyP;Matney,JacobE;Williams,AuniC;Kleweno,TalynE;Copp,StevenW
运动升压反射是由收缩的骨骼肌内的机械和代谢信号引起的反馈自主和心血管控制机制。在外周动脉疾病（PAD）患者和股动脉长期结扎的模拟PAD大鼠模型中，反射的机械敏感成分（机械反射）被夸大。环氧合酶活性的产物已显示出慢性致敏PAD中的机械反射，但介导致敏的肌肉传入受体的身份尚不清楚。我们假设，将内过氧化物4受体（EP 4-R）拮抗剂L161982或血栓烷A2受体（TxA 2-R）拮抗剂达曲班注射到后肢的动脉供应中将减少对重复性，动态后肢骨骼肌牵张在实验前约72小时结扎股动脉的大鼠中（孤立的机械反射激活模型），但在自由灌注股动脉的大鼠中则没有。结果发现，阻断EP_（4-R）对自由灌流（n= 6，前：14 ± 2，后：15 ± 2 mmHg，P= 0.97）和结扎（n= 8，前：29 ± 4，后：29 ± 6 mmHg，P= 0.98）大鼠牵张的升压反应（峰值Δ平均动脉压）无影响。阻断TxA_2-R对自由灌流大鼠牵张性升压反应无影响（n= 6，前：16 ± 3，后：17 ± 4 mmHg，P= 0.99），但明显降低结扎大鼠牵张性升压反应（n= 11，前：29 ± 4，后：17 ± 5 mmHg，P< 0.01）。我们的结论是，TxA 2-Rs有助于慢性机械反射敏化在慢性股动脉结扎大鼠模型的模拟PAD.NEW & NOTEWORTHWe表明，血栓素A2受体，但不是内过氧化物4受体，对感觉末梢的细纤维肌肉传入有助于慢性敏化的肌肉机械反射在大鼠股动脉结扎（模型模拟外周动脉疾病）。这些数据可能对我们理解外周动脉疾病患者运动期间的血压控制具有重要意义。
The exercise pressor reflex is a feedback autonomic and cardiovascular control mechanism evoked by mechanical and metabolic signals within contracting skeletal muscles. The mechanically sensitive component of the reflex (the mechanoreflex) is exaggerated in patients with peripheral artery disease (PAD) and in a rat model of simulated PAD in which a femoral artery is chronically ligated. Products of cyclooxygenase enzyme activity have been shown to chronically sensitize the mechanoreflex in PAD, but the identity of the muscle afferent receptors that mediate the sensitization is unclear. We hypothesized that injection of the endoperoxide 4 receptor (EP4-R) antagonist L161982 or the thromboxane A2receptor (TxA2-R) antagonist daltroban into the arterial supply of the hindlimb would reduce the pressor response to repetitive, dynamic hindlimb skeletal muscle stretch (a model of isolated mechanoreflex activation) in rats with a femoral artery that was ligated ~72 h before the experiment but not in rats with freely perfused femoral arteries. We found that EP4-R blockade had no effect on the pressor response (peak Δmean arterial pressure) to stretch in freely perfused (n= 6, pre: 14 ± 2, post: 15 ± 2 mmHg,P= 0.97) or ligated (n= 8, pre: 29 ± 4, post: 29 ± 6 mmHg,P= 0.98) rats. In contrast, TxA2-R blockade had no effect on the pressor response to stretch in freely perfused rats (n= 6, pre: 16 ± 3, post: 17 ± 4 mmHg,P= 0.99) but significantly reduced the response in ligated rats (n= 11, pre: 29 ± 4, post: 17 ± 5 mmHg,P< 0.01). We conclude that TxA2-Rs contribute to chronic mechanoreflex sensitization in the chronic femoral artery-ligated rat model of simulated PAD.NEW & NOTEWORTHYWe demonstrate that thromboxane A2receptors, but not endoperoxide 4 receptors, on the sensory endings of thin fiber muscle afferents contribute to the chronic sensitization of the muscle mechanoreflex in rats with a ligated femoral artery (a model of simulated peripheral artery disease). The data may have important implications for our understanding of blood pressure control during exercise in patients with peripheral artery disease.