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1 Division of Cardiology and 2 Molecular and Systems Pharmacology Program, Emory University, and Veterans Hospital Medical Center, Atlanta, Georgia 30322
We have shown that c-Src plays a
role in shear stress stimulation of endothelial nitric oxide synthase
(eNOS) expression in cultured cells. To examine the role of c-Src in
vivo, we exercised C57Blk/6 and c-Src heterozygous
(c-Src+/
) mice on a treadmill for 3 wk. Western analysis
demonstrated that c-Src+/ mice express less than one-half
the normal amount of c-Src. Exercise increased heart rate and blood
pressure to identical levels in both strains as determined using
radiotelemetry. Exercise training increased eNOS protein >2-fold in
the aorta and 1.7-fold in the heart in C57Blk/6 mice but had no effect
on eNOS protein levels in c-Src+/ mice. In contrast to
exercise, treatment of mice with mevastatin, which stimulates
expression of eNOS posttranscriptionally, increased eNOS protein in
both strains. Training also increased aortic extracellular superoxide
dismutase protein expression, which is regulated by nitric oxide, in
C57Blk/6 mice but not in c-Src+/mice. These data
indicate that c-Src has an important role in modulating vascular
adaptations to exercise training, in particular increasing eNOS and
extracellular superoxide dismutase protein expression.
extracellular superoxide dismutase; radiotelemetry; Western analysis; mice
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