Differential regulation of cation transport of vascular smooth muscle cells in a high glucose concentration milieu.

To gain new insights into the pathogenesis of diabetic angiopathy, the influence of high glucose concentration on cation transport of vascular smooth muscle cell (VSMC) membrane was investigated by measuring Na, K and Ca transport in serially passaged cultured VSMC. (1) Na-K pump activity, described as ouabain sensitive 86Rb uptake, and Na-K cotransport, described as bumetanide sensitive 86Rb washout of VSMC, grown in high glucose concentration medium (460 mg/dl), was lower than that grown in normal glucose concentration medium (100 mg/dl). A smaller 5-N,N-hexamethylene amiloride (HMA) sensitive 22Na uptake (Na-H antiport) in high glucose concentration medium. accounted for this difference. (2) 45Ca uptake was also smaller in VSMC cultured in high glucose concentration medium. However, the washout rate constant for 45Ca was comparable between high and normal glucose cultured VSMC. (3) Both intracellular concentration of Na and cytosolic free Ca concentration concentration ([Ca]i) of high glucose cultured VSMC were greater than normal glucose cultured VSMC. (4) Intracellular water volume based on the equilibrium distribution of 3-O-methyl-[14C]glucose was not different between normal and high glucose cultured VSMC. It is concluded that VSMC grown in high glucose concentration milieu manifests a decreased Na-K, and Ca transport in conjunction with an increase in intracellular concentration of Na and [Ca]i. These results suggest that high glucose, per se, may alter membrane permeability to cations, possibly leading to changes in VSMC contractility and/or proliferation. This abnormality seen in the diabetic state may closely link to the pathogenesis of diabetic angiopathy, thus as a result risking hypertension and vascular disease.