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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 ≈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 [ 3 H]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.

Dialysis clearance of cimetidine in patients receiving peritoneal dialysis, hemodialysis, and hemoperfusion was compared in stable and seriously ill patients. Two methods of determining dialysis clearance were employed, one of which was the method employed for cimetidine previously in the literature. Cimetidine clearance was lowest for peritoneal dialysis (5 ml/min), intermediate for hemodialysis (28 ml/min), and greatest for hemoperfusion (85 ml/min). Using both methods to calculate dialysis clearance, we found that cimetidine clearance during dialysis has been overestimated. In addition, pharmacokinetic analysis revealed that peritoneal and hemodialysis apparently removed cimetidine from the central compartment only, whereas hemoperfusion apparently removed drug from the peripheral compartment as well. A possible mechanism to explain this difference is based on the observation that hemodynamic changes occur during hemodialysis that may not be seen during hemoperfusion. No dosage adjustment need be made when patients receiving cimetidine undergo any form of dialysis; hemoperfusion may be of some benefit in removing drug from the central as well as tissue compartments in an acute overdose situation.