Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels
Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels
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DOI：
10.1152/ajpregu.00294.2018
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发表时间：
2019-05-01
影响因子：
2.8
通讯作者：
Stone, Audrey J.
中科院分区：
文献类型：
--
作者：
Grotle, Ann-Katrin;Garcia, Elizabeth A.;Stone, Audrey J.
最近的研究结果表明，肌肉收缩引起1型糖尿病（T1 DM）大鼠的过度升压反应;然而，目前尚不清楚通常通过拉伸跟腱刺激的机械反射是否有助于这种异常反应。此外，在细纤维传入末梢上发现的机械门控压电通道在诱发T1 DM中的机械反射中的作用也是未知的。因此，在雄性和雌性链脲佐菌素（STZ，50 mg/kg）诱导的T1 DM和健康对照（CTL）大鼠，我们检查了升压和心脏加速器反应的肌腱拉伸在疾病的早期阶段。为了确定压电通道的作用，将选择性压电通道抑制剂GsMTx-4注射到后肢的动脉供应中。在麻醉的去大脑大鼠注射STZ后1周，我们拉伸跟腱30秒，测量升压和心脏加速器反应。然后，我们比较了升压和心脏加速器的反应，肌腱拉伸之前和之后GsMTx-4注射（10 μ g/100 ml）。我们发现，（平均动脉压变化）反应[STZ为41 +/- 5 mmHg（n = 15），CTL为18 +/- 3 mmHg（n = 11（P < 0.01）]和心脏加速器在STZ大鼠中，对肌腱拉伸的（心率变化）反应[STZ为18 +/-4次/分钟（n = 15），CTL为8 +/-2次/分钟（n = 11）（P < 0.05）]被夸大。局部注射GsMTx-4可减弱STZ大鼠对肌腱牵拉的升压反应[GsMTx-4前为55 +/- 7 mmHg（n = 6），GsMTx-4后为27 +/- 9 mmHg（n = 6）（P < 0.01）]，但对心脏加速器反应无影响，对CTL大鼠的两种反应均无影响。这些数据表明，T1 DM夸大了肌腱拉伸的机械反射反应，压电通道在这种夸张中发挥作用。
Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in anesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 mu g/100 ml). We found that the pressor (change in mean arterial pressure) response [41 +/- 5 mmHg (n = 15) for STZ and 18 +/- 3 mmHg (n = 11) for CTL (P < 0.01)] and cardioaccelerator (change in heart rate) response [18 +/- 4 beats/min for STZ (n = 15) and 8 +/- 2 beats/min (n = 11) for CTL (P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 +/- 7 mmHg (n = 6) before and 27 +/- 9 mmHg (n = 6) after GsMTx-4 (P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.