ATP-sensitive K+ channel inhibition in rats decreases kidney and skeletal muscle blood flow without increasing sympathetic nerve discharge
ATP-sensitive K+ channel inhibition in rats decreases kidney and skeletal muscle blood flow without increasing sympathetic nerve discharge
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DOI：
10.1016/j.resp.2020.103444
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发表时间：
2020-07-01
影响因子：
2.3
通讯作者：
Kenney, Michael J.
中科院分区：
文献类型：
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作者：
Colburn, Trenton D.;Holdsworth, Clark T.;Kenney, Michael J.
ATP敏感性K+（K-ATP）通道通过局部血管超极化或交感神经抑制和交感神经血管收缩减少而参与运动诱导的骨骼肌充血。然而，平均动脉压（MAP）调节通过压力感受器和随后传出活动可能混淆血管与神经K-ATP通道功能的评估。我们假设通过格列本脲（GLI）抑制全身性K-ATP通道会增加MAP而不增加交感神经放电（SND）。在麻醉的雄性大鼠（n = 12）和去窦弓神经（SAD; n = 4）中测量腰和肾神经SND，并在清醒大鼠（n = 6）中评估血流量（BF）和血管传导性（VC）。GLI可增加正常大鼠的MAP（p < 0.05），短暂降低HR（p < 0.05），但对SAD大鼠无影响。肾脏（~ 30%）和腰椎（~ 40%）Δ SND在完整大鼠中降低，但在SAD大鼠中增加（类似于40%和20%; p < 0.05）。肾脏和后肢骨骼肌BF和VC降低（p < 0.05）。因此，由于K-ATP抑制降低SND，GLI诱导的血流量减少不能由交感神经活性增强引起。
ATP-sensitive K+ (K-ATP) channels contribute to exercise-induced hyperemia in skeletal muscle either locally by vascular hyperpolarization or by sympathoinhibition and decreased sympathetic vasoconstriction. However, mean arterial pressure (MAP) regulation via baroreceptors and subsequent efferent activity may confound assessment of vascular versus neural K-ATP channel function. We hypothesized that systemic K-ATP channel inhibition via glibenclamide (GLI) would increase MAP without increasing sympathetic nerve discharge (SND). Lumbar and renal nerve SND were measured in anesthetized male rats with intact baroreceptors (n = 12) and sinoaortic denervated (SAD; n = 4) counterparts and blood flow (BF) and vascular conductance (VC) assessed in conscious rats (n = 6). GLI increased MAP (p < 0.05) and transiently decreased HR in intact (p < 0.05), but not SAD rats. Renal (- 30 %) and lumbar (-40 %) Delta SND decreased in intact but increased in SAD rats (similar to 40 % and 20 %; p < 0.05). BF and VC decreased in kidneys and total hindlimb skeletal muscle (p < 0.05). Thus, because K-ATP inhibition decreases SND, GLI-induced reductions in blood flow cannot result from enhanced sympathetic activity.