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1 Angiogenesis Research Group,
Rat extensor digitorum longus muscles
were overloaded by stretch after removal of the synergist tibialis
anterior muscle to determine the relationship between capillary growth,
muscle blood flow, and presence of growth factors. After 2 wk,
sarcomere length increased from 2.4 to 2.9 µm. Capillary-to-fiber
ratio, estimated from alkaline phosphatase-stained frozen sections, was
increased by 33% (P < 0.0001) and
60% (P < 0.01), compared with
control muscles (1.44 ± 0.06) after 2 and 8 wk, respectively. At 2 wk, the increased capillary-to-fiber ratio was not associated with any
changes in mRNA for basic fibroblast growth factor (FGF-2) or its
protein distribution. FGF-2 immunoreactivity was present in nerves and
large blood vessels but was negative in capillaries, whereas the
activity of low-molecular endothelial-cell-stimulating angiogenic
factor (ESAF) was 50% higher in stretched muscles. Muscle blood flows
measured by radiolabeled microspheres during contractions were not
significantly different after 2 or 8 wk (132 ± 37 and 177 ± 22 ml · min
1 · 100 g
1, respectively) from
weight-matched controls (156 ± 12 and 150 ± 10 ml · min
1 · 100 g
1, respectively).
Resistance to fatigue during 5-min isometric contractions (final/peak
tension × 100) was similar in 2-wk overloaded and contralateral
muscles (85 vs. 80%) and enhanced after 8 wk to 92%, compared with
77% in contralateral muscles and 67% in controls. We conclude that
increased blood flow cannot be responsible for initiating expansion of
the capillary bed, nor does it explain the reduced fatigue within
overloaded muscles. However, stretch can present a mechanical stimulus
to capillary growth, acting either directly on the capillary abluminal
surface or by upregulating ESAF, but not FGF-2, in the extracellular matrix.
synergist extirpation; angiogenesis; growth factors; blood flow; microspheres; fatigue
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