NITRIC OXIDE, EXERCISE, HYPEREMIA, AND 0XYGEN UPTAKE

一氧化氮(NO)是血管功能的重要生理调节因子。最近的数据表明，NO在组织氧耗的调节中也起着重要作用。NO在人体骨骼肌充血和氧耗中的作用尚不清楚。关于运动期间骨骼肌中NO的产生是否会增加，目前还没有明确的数据。NO是否参与调节人体在休息和运动过程中的骨骼肌氧摄取也不清楚。拟议的实验将测试1)动态运动中骨骼肌中NO的产生是否增加；2)运动中骨骼肌中产生的NO是否与运动相关的充血有关；3)内源性NO是否调节安静和运动中的骨骼肌耗氧量。我们将使用稳定同位素技术测量精氨酸到瓜氨酸的转化，作为内皮NO产生的直接指标；我们还将通过输注L-NMMA来阻断NO的合成。运动肌肉耗氧量(VO2)将直接测量，全身VO2将在口腔测量。拟议的实验设计的优势在于，我们将研究人类运动过程中循环控制的基本机制。这些实验的结果将为NO在调节人体骨骼肌血流和氧耗中的机制作用提供重要的新信息。

Nitric oxide (NO) is an important physiological regulator of vascular function. Recent data indicate that NO also has a significant role in the modulation of tissue oxygen consumption. The roles of NO in skeletal muscle hyperemia and oxygen consumption in humans are unclear. There are no definitive data regarding whether NO production increases in skeletal muscle during exercise. Whether NO contributes to the regulation of skeletal muscle oxygen uptake at rest and during exercise in humans is also unclear. The proposed experiments will test 1) whether NO production in skeletal muscle increases during dynamic exercise; 2) whether NO produced during exercise in skeletal muscle contributes to the hyperemia associated with exercise; and 3) whether endogenous NO modulates skeletal muscle oxygen consumption at rest and during exercise. We will measure the conversion of arginine to citrulline, using stable isotope techniques, as a direct index of endothelial NO production; we will also use blockade of NO synthesis via infusion of L-NMMA. Exercising muscle oxygen consumption (VO2) will be measured directly and whole body VO2 will be measured at the mouth. The strength of the proposed experimental design is that we will study basic mechanisms of circulatory control during exercise in humans. The results of these experiments will provide important new information about the mechanistic role of NO in the regulation of skeletal muscle blood flow and oxygen consumption in humans.