Functional hyperemia of skeletal muscle: role of endothelium

The role of the endothelium and endothelium-derived vasoactive factors in the development of skeletal muscle functional hyperemia was studied. Experiments were performed in anesthetized dogs. Functional hyperemia of isometrically contracted gastrocnemius muscle was produced by direct electric stimulation. Five series of experiments were conducted to investigate the effect of (a) de-endothelialization of gastrocnemius vessels, (b) inhibition of prostanoids biosynthesis by indomethacin, (c) inhibition by gossipol of lipoxygenase, which mediates biosynthesis of endothelium-derived relaxing factor (EDRF), (d) inhibition of cGMP formation by methylene blue, and (e) stimulation of EDRF biosynthesis of L-arginine. The gastrocnemius muscle work was accompanied by an increase in blood flow by 6.8 +/- 0.6 ml/min/N (8 Hz) and by 2.5 +/- 0.2 ml/min/N) (40 Hz). Chemical deendothelialization of gastrocnemius vessels decreased functional hyperemia, and blood flow increased by only 1.2 +/- 0.3 ml/min/N (8 Hz) and by 0.5 +/- 0.1 ml/min/N (40 Hz). Cyclooxygenase inhibition by indomethacin had no significant effect on functional hyperemia, whereas methylene blue and gossipol inhibited functional hyperemia by 4.2- and 6.6-fold, respectively, and L-arginine significantly elevated blood flow by 12.6 +/- 1.4 ml/min/N (8 Hz) and by 3.5 +/- 0.2 ml/min/N (40 Hz) during skeletal muscle work. Thus, it can be concluded that the endothelium plays an important role in functional hyperemia of skeletal muscle, probably through the release of EDRF.