Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats
Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats
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DOI：
10.1113/jp282981
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发表时间：
2022-05-24
影响因子：
5.5
通讯作者：
Pearson，James T.
中科院分区：
文献类型：
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作者：
Sonobe，Takashi;Tsuchimochi，Hirotsugu;Pearson，James T.
在阻力动脉中，内皮依赖性超极化（EDH）介导的血管舒张在糖尿病中受到抑制。我们假设KCa通道衍生的EDH的下调减少了糖尿病中运动诱导的血管舒张和血流再分布。为了验证这一假设，我们评估了血管功能，后肢肌肉收缩，和钾钙通道的贡献麻醉ZFDM，代谢性疾病大鼠2型糖尿病。我们还测试了运动训练是否改善了血管反应。采用活体微血管造影技术，观察坐骨神经刺激（40 Hz）诱发的肌肉节律性收缩（每3s强直0.5s，共20次）前后后肢血管的变化。同时用超声流量计测量收缩后肢股动脉血流量。KCa通道的贡献进行了研究，在存在和不存在的apamin和charybdotoxin。我们发现，血管和血液流动的肌肉收缩反应显着受损的水平ZFDM fa/fa大鼠的小动脉节段相比，其瘦对照fa/+大鼠。在fa/fa中KCa通道的贡献也小于fa/+大鼠。在fa/fa大鼠中进行12周的低强度运动训练，表明血管和血流对肌肉收缩的反应发生了微小变化。然而，在运动训练的fa/fa大鼠中，肌肉收缩反应中的KCa衍生成分远高于久坐的fa/fa大鼠。这些数据表明，运动训练增加了KCa通道在内皮依赖性血管舒张机制中的贡献，以维持血管和血流对这种代谢疾病大鼠模型中肌肉收缩的反应。关键点2型糖尿病中的微血管功能障碍损害了运动期间的血流再分布，限制了骨骼肌的性能，并可能导致早期疲劳。内皮依赖性超极化（EDH），在此，我们报告，与久坐大鼠相比，ZFDM大鼠的低强度运动训练增加了KCa通道衍生成分对肌肉收缩的血管舒张反应，部分原因是KCNN 3表达增加。这些结果表明，低强度运动训练改善了代谢性骨骼肌收缩中的血流再分布。通过上调EDH而导致糖尿病。
AbstractIn resistance arteries, endothelium‐dependent hyperpolarization (EDH)‐mediated vasodilatation is depressed in diabetes. We hypothesized that downregulation of KCa channel derived EDH reduces exercise‐induced vasodilatation and blood flow redistribution in diabetes. To test this hypothesis, we evaluated vascular function in response to hindlimb muscle contraction, and the contribution of KCa channels in anaesthetised ZFDM, metabolic disease rats with type 2 diabetes. We also tested whether exercise training ameliorated the vascular response. Usingin vivomicroangiography, the hindlimb vasculature was visualized before and after rhythmic muscle contraction (0.5 s tetanus every 3 s, 20 times) evoked by sciatic nerve stimulation (40 Hz). Femoral blood flow of the contracting hindlimb was simultaneously measured by an ultrasonic flowmeter. The contribution of KCa channels was investigated in the presence and absence of apamin and charybdotoxin. We found that vascular and blood flow responses to muscle contraction were significantly impaired at the level of small artery segments in ZFDM fa/fa rats compared to its lean control fa/+ rats. The contribution of KCa channels was also smaller in fa/fa than in fa/+ rats. Low‐intensity exercise training for 12 weeks in fa/fa rats demonstrated minor changes in the vascular and blood flow response to muscle contraction. However, the KCa‐derived component in the response to muscle contraction was much greater in exercise trained than in sedentary fa/fa rats. These data suggest that exercise training increases the contribution of KCa channels among endothelium‐dependent vasodilatory mechanisms to maintain vascular and blood flow responses to muscle contraction in this metabolic disease rat model.Key pointsMicrovascular dysfunction in type 2 diabetes impairs blood flow redistribution during exercise and limits the performance of skeletal muscle and may cause early fatigability.Endothelium‐dependent hyperpolarization (EDH), which mediates vasodilatation in resistance arteries, is known to be depressed in animals with diabetes.Here, we report that low‐intensity exercise training in ZFDM rats increased the KCa channel‐derived component in the vasodilator responses to muscle contraction compared to that in sedentary rats, partly as a result of the increase in KCNN3 expression.These results suggest that low‐intensity exercise training improves blood flow redistribution in contracting skeletal muscle in metabolic disease with diabetes via upregulation of EDH.