Mortensen Stefan P, González-Alonso José, Damsgaard Rasmus, Saltin Bengt, Hellsten Ylva
The Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark.
J Physiol. 2007 Jun 1;581(Pt 2):853-61. doi: 10.1113/jphysiol.2006.127423. Epub 2007 Mar 8.
Prostaglandins, nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs) are substances that have been proposed to be involved in the regulation of skeletal muscle blood flow during physical activity. We measured haemodynamics, plasma ATP at rest and during one-legged knee-extensor exercise (19 +/- 1 W) in nine healthy subjects with and without intra-arterial infusion of indomethacin (Indo; 621 +/- 17 microg min(-1)), Indo + N(G)-monomethyl-L-arginine (L-NMMA; 12.4 +/- 0.3 mg min(-1)) (double blockade) and Indo + L-NMMA + tetraethylammonium chloride (TEA; 12.4 +/- 0.3 mg min(-1)) (triple blockade). Double and triple blockade lowered leg blood flow (LBF) at rest (P<0.05), while it remained unchanged with Indo. During exercise, LBF and vascular conductance were 2.54 +/- 0.10 l min(-1) and 25 +/- 1 mmHg, respectively, in control and they were lower with double (33 +/- 3 and 36 +/- 4%, respectively) and triple (26 +/- 4 and 28 +/- 3%, respectively) blockade (P<0.05), while there was no difference with Indo. The lower LBF and vascular conductance with double and triple blockade occurred in parallel with a lower O(2) delivery, cardiac output, heart rate and plasma [noradrenaline] (P<0.05), while blood pressure remained unchanged and O(2) extraction and femoral venous plasma [ATP] increased. Despite the increased O(2) extraction, leg was 13 and 17% (triple and double blockade, respectively) lower than control in parallel to a lower femoral venous temperature and lactate release (P<0.05). These results suggest that NO and prostaglandins play important roles in skeletal muscle blood flow regulation during moderate intensity exercise and that EDHFs do not compensate for the impaired formation of NO and prostaglandins. Moreover, inhibition of NO and prostaglandin formation is associated with a lower aerobic energy turnover and increased concentration of vasoactive ATP in plasma.
前列腺素、一氧化氮（NO）和内皮衍生超极化因子（EDHFs）被认为参与了体力活动期间骨骼肌血流的调节。我们在9名健康受试者中测量了静息状态以及单腿伸膝运动（19±1瓦）期间的血流动力学、血浆ATP，这些受试者接受了动脉内输注吲哚美辛（Indo；621±17微克·分钟⁻¹）、Indo + N⁰-单甲基-L-精氨酸（L-NMMA；12.4±0.3毫克·分钟⁻¹）（双重阻断）和Indo + L-NMMA + 四乙铵氯化物（TEA；12.4±0.3毫克·分钟⁻¹）（三重阻断）。双重和三重阻断降低了静息状态下的腿部血流量（LBF）（P<0.05），而Indo处理时LBF保持不变。运动期间，对照组的LBF和血管传导率分别为2.54±0.10升·分钟⁻¹和25±1毫米汞柱，双重阻断（分别为33±3%和36±4%）和三重阻断（分别为26±4%和28±3%）时LBF和血管传导率降低（P<0.05），而Indo处理时无差异。双重和三重阻断时较低的LBF和血管传导率与较低的氧输送、心输出量、心率和血浆[去甲肾上腺素]同时出现（P<0.05），而血压保持不变，氧摄取和股静脉血浆[ATP]增加。尽管氧摄取增加，但与较低的股静脉温度和乳酸释放同时出现，腿部血流量比对照组低13%和17%（分别为三重和双重阻断）（P<0.05）。这些结果表明，NO和前列腺素在中等强度运动期间的骨骼肌血流调节中起重要作用，并且EDHFs不能补偿NO和前列腺素形成受损的情况。此外，抑制NO和前列腺素形成与较低的有氧能量转换和血浆中血管活性ATP浓度增加有关。
