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

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 deter-mined 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 1RBC(-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-dfin 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.