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Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623
Vascular endothelial growth factor
(VEGF), basic fibroblast growth factor (bFGF), and transforming growth
factor-
1 (TGF-1) mRNA increase in rat
skeletal muscle in response to a single acute exercise bout. Nitric
oxide (NO) is released locally by muscle vascular endothelium
and muscle fibers during exercise, contributes to the blood flow
response to exercise, and regulates mitochondrial respiration. We
hypothesized that a reduction in NO production, via NO synthase
inhibition, would demonstrate a link between NO and the VEGF, bFGF, and
TGF-1 gene responses to exercise. To investigate this
hypothesis, 9-wk-old female Wistar rats were divided into eight
treatment groups (n = 6 each): 1) saline + rest,
2) saline + exercise, 3) 30 mg/kg
N
-nitro-L-arginine methyl ester
(L-NAME, a known NOS inhibitor) + rest, 4) 30 mg/kg
L-NAME + exercise, 5) 300 mg/kg L-NAME + rest, 6) 300 mg/kg L-NAME + exercise, 7)
300 mg/kg N-nitro-D-arginine methyl
ester (D-NAME, inactive enantiomer of L-NAME) + rest, and 8) 300 mg/kg D-NAME + exercise. Exercise
consisted of 1 h of running at 20 m/min on a 10° incline. VEGF,
TGF-1, and bFGF mRNA from left gastrocnemius were
analyzed by quantitative Northern blot. Submaximal exercise for 1 h
increased VEGF mRNA 4.2-fold and TGF-1 mRNA 1.5-fold in
untreated rats but did not increase bFGF mRNA. The exercise-induced
increase in VEGF mRNA was attenuated ~50% by 30 and 300 mg/kg
L-NAME; the TGF-1 mRNA increase was
unaffected by 300 mg/kg L-NAME. In addition, 300 mg/kg
D-NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg L-NAME had no effect
on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in
VEGF transcription or by increases in the VEGF mRNA half-life.
vascular endothelial growth factor; transforming growth
factor-1; basic fibroblast growth factor; N-nitro-L-arginine methyl ester; N-nitro-D-arginine methyl ester
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