Capillary response to skeletal muscle contraction: evidence that redundancy between vasodilators is physiologically relevant during active hyperaemia
Capillary response to skeletal muscle contraction: evidence that redundancy between vasodilators is physiologically relevant during active hyperaemia
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DOI：
10.1113/jp275467
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发表时间：
2018-04-15
影响因子：
5.5
通讯作者：
Murrant, Coral L.
中科院分区：
文献类型：
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作者：
Lamb, Iain R.;Novielli, Nicole M.;Murrant, Coral L.
我们试图确定血管扩张剂之间的冗余是否与活动性充血的生理相关。由于血管扩张剂之间的抑制性相互作用是冗余的指示，我们测试了参与介导活性充血的血管扩张剂（钾（K+）、腺苷（ADO）和一氧化氮（NO））是否通过直接应用药理学试剂和在肌肉收缩期间抑制彼此的血管扩张作用。用仓鼠提睾肌和活体显微镜，在无和有第二种血管扩张剂（10（-7）mS-亚硝基-N-乙酰青霉胺（SNAP），10（-7）mADO，10 mmKCl）的情况下，用一种血管扩张剂局部刺激毛细血管，并观察控制刺激毛细血管灌注的相关上游4A小动脉的反应。我们发现，KCl显着衰减SNAP和ADO诱导的血管舒张分别约为49.7%和128.0%，ADO显着衰减KCl和SNAP诱导的血管舒张分别约为94.7%和59.6%。NO使KCl舒张血管的作用减弱93.8%。此外，在肌肉收缩过程中，我们发现，抑制NO的生产，使用L-N-G-硝基精氨酸甲酯和抑制ADO受体，使用黄嘌呤胺同源物是有效的抑制收缩诱导的血管舒张，但只有在存在的K+释放通道抑制。因此，只有当抑制性血管扩张剂K+被阻断时，第二种血管扩张剂NO或ADO才能产生有效的血管扩张作用。因此，我们表明，在毛细血管的水平上，特异性血管扩张剂之间存在抑制性相互作用。此外，在肌肉收缩期间可以观察到这些抑制，表明血管扩张剂之间的冗余是生理相关的，并且在活动性充血期间影响血管扩张。
We sought to determine if redundancy between vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between vasodilators are indicative of redundancy, we tested whether vasodilators implicated in mediating active hyperaemia (potassium (K+), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10(-7) mS-nitroso-N-acetylpenicillamine (SNAP), 10(-7) m ADO, 10mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by approximate to 49.7% and approximate to 128.0% respectively and ADO significantly attenuated KCl- and SNAP-induced vasodilatations by approximate to 94.7% and approximate to 59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l-N-G-nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction-induced vasodilatation but only in the presence of K+ release channel inhibition. Thus, only when the inhibiting vasodilator K+ was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia.