ANGIOGENIC GROWTH-FACTOR MESSENGER-RNA RESPONSES TO PASSIVE AND CONTRACTION-INDUCED HYPERPERFUSION IN SKELETAL-MUSCLE

It has been proposed that, in skeletal muscle, the angiogenic response to exercise may be signaled by the increase in muscle blood flow, via biomechanical changes in the microcirculation (increased shear stress and/or wall tension). To examine this hypothesis, we compared the cha nge in abundance of vascular endothelial growth factor (VEGF), basic f ibroblast growth factor (bFGF), and transforming growth factor-beta(1) (TGF-beta(1)) mRNA in skeletal muscles of the canine leg after 1 h of pump-controlled high blood flow alone (passive hyperperfusion; protoc ol A) and electrical stimulation of the femoral and sciatic nerves pro ducing muscle contraction (protocol B). The increase in leg blood flow (5.4- and 5.9-fold change from resting values, respectively) was simi lar in both groups. Passive hyperperfusion alone did not increase mess age abundance for VEGF (ratio of mRNA to 188 signals after vs. before hyperperfusion, 0.94 +/- 0.08) or bFGF (1.08 +/- 0.05) but slightly in creased that of TGF-beta(1) (1.14 +/- 0.07; P < 0.03). In contrast, as previously found in the rat, electrical stimulation provoked more tha n a threefold increase in VEGF mRNA abundance (3.40 +/- 1.45; P < 0.02 ). However, electrical stimulation produced no significant changes in either bFGF (1.16 +/- 0.13) or TGF-beta(1) (1.31 +/- 0.27). These resu lts suggest that the increased muscle blood flow of exercise does not account for the increased abundance of these angiogenic growth factor mRNA levels in response to acute exercise. We speculate that other fac tors, such as local hypoxia, metabolite concentration changes, or mech anical effects of contraction per se, may be responsible for the effec ts of exercise.