Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle.
Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle.
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人体骨骼肌短暂收缩后快速血管舒张的机制。
DOI：
10.1152/ajpheart.00298.2013
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Dinenno,FrankA
中科院分区：
文献类型：
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作者：
Crecelius,AnneR;Kirby,BrettS;Luckasen,GaryJ;Larson,DennisG;Dinenno,FrankA
在人类短暂的前臂收缩后，可以观察到骨骼肌血流量的单相增加，但潜在的血管信号通路在很大程度上仍未确定。来自实验动物的证据表明，血管扩张是通过K+介导的平滑肌超极化所必需的，而人类的数据表明，一氧化氮(NO)或血管扩张前列腺素(PGs)几乎没有独立作用。我们测试了一种假设，即K+介导的血管超极化是人类快速血管扩张的基础，联合抑制NO和PGs对这种反应的影响很小。我们测量了16名年轻人在10%、20%和40%最大自主收缩时的前臂血流(多普勒超声)，并计算了10名S和30名S在单次1-S收缩前、后的血管电导。为抑制K+介导的血管扩张，动脉内注入BaCl2和哇巴因分别抑制内向整流性K+通道和Na+-K+-ATPase。对NO和PG合成的联合抑制分别通过L-单甲基-L-精氨酸和酮咯酸(环氧合酶)发生。在方案1(n=8)中，BaCl2+哇巴因降低了所有强度的峰值血管扩张(范围：30-45%，P<0.05)和总的收缩后血管扩张(曲线下面积，∼为对照的55-75%)。与我们的假设相反，L-甲基丙烯酸甲酯+酮咯酸有进一步的影响(峰值：∼为对照的60%，曲线下面积：∼为对照的80%)。在方案2(n=8)中，抑制剂的顺序颠倒了，结果非常相似。我们的结论是，K+介导的超极化以及NO和PGs共同作用于收缩诱导的快速血管扩张，而抑制这些信号通路几乎消除了人类的这种现象。
A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K+-mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K+-mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K+-mediated vasodilation, BaCl2and ouabain were infused intra-arterially to inhibit inwardly rectifying K+channels and Na+-K+-ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred viaNG-monomethyl-l-arginine (l-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. Inprotocol 1(n= 8), BaCl2+ ouabain reduced peak vasodilation (range: 30–45%,P< 0.05) and total postcontraction vasodilation (area under the curve, ∼55–75% from control) at all intensities. Contrary to our hypothesis,l-NMMA + ketorolac had a further impact (peak: ∼60% and area under the curve: ∼80% from control). Inprotocol 2(n= 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K+-mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.