Bradykinin 2 receptors contribute to the exaggerated exercise pressor reflex in a rat model of simulated peripheral artery disease.
Bradykinin 2 receptors contribute to the exaggerated exercise pressor reflex 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，缓激肽 2 受体会导致运动升压反射过度。
DOI：
10.1152/ajpregu.00274.2022
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Copp,StevenW
中科院分区：
文献类型：
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作者：
Butenas,AlecLE;Rollins,KorynneS;Williams,AuniC;Copp,StevenW
采用大鼠股动脉结扎72h建立模拟外周动脉病(PAD)模型，观察缓激肽2(B2)受体在运动加压反射过度中的作用。我们假设，在去大脑、结扎股动脉的未麻醉大鼠，后肢动脉注射HOE-140(100 ng，B2受体拮抗剂)可降低30 S电诱导的1 Hz后肢骨骼肌收缩和30 S 1 Hz后肢骨骼肌牵拉的升压反应(这是一种从收缩诱导的代谢物产生中分离出来的机械反射激活模型)。我们假设HOE-140对假手术“自由灌流”的大鼠没有影响。在自由灌流大鼠(n=4)和结扎大鼠(n=4)上，我们首次证实了有效的B2受体阻滞剂，证明HOE-140注射显著降低了由后肢动脉注射缓激肽引起的平均动脉压峰值升高(峰值Δ图)(P<；0.05)。在随后的实验中，我们发现HOE-140降低了结扎大鼠肌肉收缩的峰值ΔMAP(n=14；对照组：23 ± 2；HOE-140：17 ± 2；P=0.03)，但不能降低自由灌流的大鼠(n=7；对照组：17 ± 3；HOE-140：18 ± 4 mm Hg；P=0.65)。此外，HOE-140对结扎大鼠(n=14；对照组：37 ± 4；HOE-140：32 ± 5 ；P=0.13)的ΔMAP峰值反应无影响，但在动作的末次∼20 S时，血压信号下的积分面积减小。这些数据表明，B2受体参与了模拟PAD大鼠过度的运动加压反射，这种贡献包括在机械激活的通道/传入的慢性敏化中所起的适度作用。
We investigated the role played by bradykinin 2 (B2) receptors in the exaggerated exercise pressor reflex in rats with a femoral artery ligated for 72 h to induce simulated peripheral artery disease (PAD). We hypothesized that in decerebrate, unanesthetized rats with a ligated femoral artery, hindlimb arterial injection of HOE-140 (100 ng, B2 receptor antagonist) would reduce the pressor response to 30 s of electrically induced 1 Hz hindlimb skeletal muscle contraction, and 30 s of 1 Hz hindlimb skeletal muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production). We hypothesized no effect of HOE-140 in sham-operated “freely perfused” rats. In both freely perfused (n= 4) and “ligated” (n= 4) rats, we first confirmed efficacious B2 receptor blockade by demonstrating that HOE-140 injection significantly reduced (P< 0.05) the peak increase in mean arterial pressure (peak ΔMAP) in response to hindlimb arterial injection of bradykinin. In subsequent experiments, we found that HOE-140 reduced the peak ΔMAP response to muscle contraction in ligated (n= 14; control: 23 ± 2; HOE-140: 17 ± 2 mmHg;P= 0.03) but not freely perfused rats (n= 7; control: 17 ± 3; HOE-140: 18 ± 4 mmHg;P= 0.65). Furthermore, HOE-140 had no effect on the peak ΔMAP response to stretch in ligated rats (n= 14; control: 37 ± 4; HOE-140: 32 ± 5 mmHg;P= 0.13) but reduced the integrated area under the blood pressure signal over the final ∼20 s of the maneuver. The data suggest that B2 receptors contribute to the exaggerated exercise pressor reflex in rats with simulated PAD, and that contribution includes a modest role in the chronic sensitization of the mechanically activated channels/afferents that underlie mechanoreflex activation.