Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium-ion concentration and poor glycaemic control in NIDDM

Abstract

Aims. To explore the mechanisms underlying the impaired erythrocyte deformability (RBC-df) in diabetic patients, the relationship between erythrocyte intracellular free calcium-ion concentration ([Ca2+](i)) and RBC-df, and the effects of Ca2+-channel blocker on [Ca2+](i) and RBC-df were evaluated. Methods. Forty-eight patients with NIDDM and 24 control subjects were enrolled in this study. [Ca2+](i) was determined using fura-2, and RBC-df by filtration method expressed as Deformability Index (DI). Erythrocytes were treated with nisoldipine to evaluate the effects of a Ca2+-channel blocker. Results. [Ca2+](i) was significantly higher (82.6 (78.0-87.2) vs 76.6 (74.3-81.2) nmol IRBC-1, P < 0.001), and DI was significantly lower (0.14 (0.09-0.28) vs 0.22 (0.16-0.28), P < 0.01) in NIDDM than in controls. There was a significant correlation between HbA(1c), and [Ca2+](i) (r = 0.38, P < 0.01), between HbA(1c), and DI (r = -0.51, P < 0.01), and between [Ca2+](i) and DI (r = -0.42, P < 0.01). Stepwise multiple regression analysis revealed HbA(1c), and [Ca2+](i) as independent determinants for the impaired RBC-df. Nisoldipine treatment in vitro significantly decreased [Ca2+](i), and significantly improved RBC-df. Conclusions. These data indicate that the impaired RBC-df in NIDDM may at least partly be attributed to the elevated [Ca2+](i) and poor glycaemic control. In addition favorable effects of a Ca2+-channel blocker on both [Ca2+](i) and RBC-df have been demonstrated.