VEGF GENE-EXPRESSION IS UP-REGULATED IN ELECTRICALLY STIMULATED RAT SKELETAL-MUSCLE

Vascular endothelial growth factor (VEGF; also called vascular permeab ility factor) is a secreted mitogen with distinct target cell specific ity for vascular endothelial cells. Hypoxia upregulates VEGF expressio n, making it a likely mediator of the angiogenesis that occurs in poor ly perfused tissues. The purpose of this study was to determine whethe r VEGF gene expression is upregulated in chronically stimulated skelet al muscles, where hypoxia is thought to trigger the growth of blood ve ssels. The right anterior tibialis and extensor digitorum longus muscl es of 12 rats were stimulated electrically (10 Hz, 300 mu s pulses) fo r up to 21 days by way of the peroneal motor nerve. The contralateral muscles served as control. Northern analysis showed that VEGF mRNA lev els increased by approximately sixfold after 4 days of stimulation and then decreased gradually over the next several days. VEGF mRNA levels were still elevated by two- to threefold after 21 days of stimulation . Higher VEGF mRNA levels in the early stages of muscle stimulation an d gradually decreasing levels in later stages are consistent with a me tabolic hypothesis in which tissue oxygenation controls VEGF expressio n. These studies support the hypothesis that VEGF has a physiological role in promoting angiogenesis in stimulated skeletal muscle.