Holdsworth Clark T, Ferguson Scott K, Colburn Trenton D, Fees Alexander J, Craig Jesse C, Hirai Daniel M, Poole David C, Musch Timothy I
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA.
Respir Physiol Neurobiol. 2017 Apr;238:33-40. doi: 10.1016/j.resp.2017.01.009. Epub 2017 Jan 22.
The vascular ATP-sensitive K (K) channel is a mediator of skeletal muscle microvascular oxygenation (POmv) during contractions in health. We tested the hypothesis that K channel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce POmv and exacerbate the time taken to reach the POmv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent K channel activation would oppose the effects of this inhibition. Muscle POmv (phosphorescence quenching) was measured during 180s of 1-Hz twitch contractions (∼6V) under control, glibenclamide (GLI, K channel antagonist; 5mg/kg) and pinacidil (PIN, K channel agonist; 5mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1mmHg). GLI reduced baseline POmv (control: 28.3±0.9, GLI: 24.8±1.0mmHg, p<0.05), lowered mean POmv (average POmv during the overall time taken to reach the steady-state; control: 20.6±0.6, GLI: 17.6±0.3mmHg, p<0.05), and slowed the attainment of steady-state POmv (overall mean response time; control: 66.1±10.2, GLI: 93.6±7.8s, p<0.05). PIN opposed these effects on the baseline POmv, mean POmv and time to reach the steady-state POmv (p<0.05 for all vs. GLI). Inhibition of K channels exacerbates the transient mismatch between muscle O delivery and utilization in CHF rats and this effect is opposed by PIN. These data reveal that the K channel constitutes one of the select few well-preserved mechanisms of skeletal muscle microvascular oxygenation control in CHF.
在健康状态下，血管ATP敏感性钾（K）通道是骨骼肌微血管氧合（POmv）在收缩过程中的一种介质。我们检验了这样一个假设，即K通道功能在慢性心力衰竭（CHF）中得以保留，因此抑制该通道会降低POmv，并延长斜方肌收缩过程中达到POmv稳态所需的时间。此外，我们假设随后的K通道激活会对抗这种抑制作用。在16只通过心肌梗死（冠状动脉结扎，左心室舒张末期压力：18±1mmHg）诱导出CHF的雄性Sprague-Dawley大鼠中，在对照、格列本脲（GLI，K通道拮抗剂；5mg/kg）和匹那地尔（PIN，K通道激动剂；5mg/kg）条件下，在1Hz的抽搐收缩（约6V）持续180秒期间测量肌肉POmv（磷光猝灭）。GLI降低了基线POmv（对照：28.3±0.9，GLI：24.8±1.0mmHg，p<0.05），降低了平均POmv（达到稳态所需的总时间内的平均POmv；对照：20.6±0.6，GLI：17.6±0.3mmHg，p<0.05），并减缓了POmv稳态的达到（总体平均反应时间；对照：66.1±10.2，GLI：93.6±7.8秒，p<0.05）。PIN对抗了这些对基线POmv、平均POmv和达到POmv稳态时间的影响（与GLI相比，所有情况p<0.05）。抑制K通道会加剧CHF大鼠肌肉氧输送与利用之间的短暂不匹配，而PIN可对抗这种作用。这些数据表明，K通道是CHF中骨骼肌微血管氧合控制中少数几个保存完好的机制之一。
