From the Department of Physiology and Biophysics and Center for
Excellence in Cardiovascular-Renal Research, University of Mississippi Medical
Center (Jackson).
Correspondence to Dr Thomas H. Adair, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, Mississippi 39216-4505. E-mail thadair{at}fiona.umsmed.edu
Abstract—The mechanisms of
sodium-induced myocardial hypertrophy and vascular
hypertrophy are poorly understood. We tested the hypothesis
that a high sodium concentration can directly induce cellular
hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and
vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture
of DMEM and M199 supplemented with 10% fetal bovine serum. When the
monolayers reached
© 1998 American Heart Association, Inc.
Scientific Contributions
Sodium Induces Hypertrophy of Cultured Myocardial Myoblasts and Vascular Smooth Muscle Cells
80% confluence, normal sodium medium (146
mmol/L) was replaced with high sodium media (152 mmol/L, 160
mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a
baseline concentration of 146 mmol/L to the higher concentrations
for 5 days caused dose-related increases in cell mean diameter, cell
volume, and cellular protein content in both MMbs and VSMCs. Increasing
the sodium concentration by only 4% (from 146 mmol/L to 152
mmol/L) caused the following respective changes in MMbs and VSMCs:
8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0%
increase in cell volume, and 55.7% and 46.7% increase in cellular
protein content. The rate of protein synthesis, expressed as
[3H]leucine incorporation, increased by 87% and 99% in
MMbs after exposure to 152 mmol/L and 160 mmol/L sodium,
respectively, compared with the 146-mmol/L sodium control group.
Exposure of MMbs to medium with a sodium concentration of 10% above
normal, ie, 160 mmol/L, caused a significant decrease (range, 26%
to 44%) in the rate of protein degradation at multiple time points
over a 48-hour period compared with normal sodium control cells. The
increase in cellular protein content caused by 160 mmol/L sodium
returned to normal within 3 days after MMbs were returned to a normal
sodium medium. These findings support the hypothesis that sodium has a
direct effect to induce cellular hypertrophy and may
therefore be an important determinant in causing myocardial and/or
vascular hypertrophy in subjects with increased sodium
concentration in the extracellular fluid.
Key Words: sodium • hypertrophy • myocardial myoblasts • muscle, smooth, vascular
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