SODIUM INDUCES HYPERTROPHY OF CULTURED MYOCARDIAL MYOBLASTS AND VASCULAR SMOOTH-MUSCLE CELLS

The mechanisms of sodium-induced myocardial hypertrophy and vascular h ypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonat al rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (V SMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented w ith 10% fetal bovine serum. When the monolayers reached approximate to 80% confluence, normal sodium medium (146 mmol/L) was replaced with h igh 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 M Mbs 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 cellul ar protein content. The rate of protein synthesis, expressed as [H-3]l eucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 1 46-mmol/L sodium control group. Exposure of MMbs to medium with a sodi um concentration of 10% above normal, ie, 160 mmol/L, caused a signifi cant decrease (range, 26% to 44%) in the rate of protein degradation a t multiple time points over a 48-hour period compared with normal sodi um control cells. The increase in cellular protein content caused by 1 60 mmol/L sodium returned to normal within 3 days after MMbs were retu rned 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 va scular hypertrophy in subjects with increased sodium concentration in the extracellular fluid.