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Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium‐ion concentration and poor glycaemic control in NIDDM
Author(s) -
Jun Fujita,
Kinsuke Tsuda,
Tomomi Takeda,
Yu Liu,
Shimpei Fujimoto,
Mariko Kajikawa,
Masuhiro Nishimura,
N. Mizuno,
Yoshiyuki Hamamoto,
Eri Mukai,
Tomohiko Adachi,
Yutaka Seino
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00934.x
Subject(s) - nisoldipine , medicine , erythrocyte deformability , endocrinology , calcium , chemistry , intracellular , calcium in biology , calcium channel blocker , red blood cell , biochemistry , nifedipine
Aims To explore the mechanisms underlying the impaired erythrocyte deformability (RBC‐df) in diabetic patients, the relationship between erythrocyte intracellular free calcium‐ion concentration ([Ca 2+ ]i) and RBC‐df, and the effects of Ca 2+ ‐channel blocker on [Ca 2+ ]i and RBC‐df were evaluated.Methods Forty‐eight patients with NIDDM and 24 control subjects were enrolled in this study. [Ca 2+ ]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 Ca 2+ ‐channel blocker.Results [Ca 2+ ]i was significantly higher (82.6 (78.0–87.2) vs 76.6 (74.3–81.2) nmol lRBC −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 [Ca 2+ ]i (r=0.38, P<0.01), between HbA 1c and DI (r=−0.51, P<0.01), and between [Ca 2+ ]iand DI (r=−0.42, P<0.01). Stepwise multiple regression analysis revealed HbA 1c and [Ca 2+ ]i as independent determinants for the impaired RBC‐df. Nisoldipine treatment in vitro significantly decreased [Ca 2+ ]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 [Ca 2+ ]i and poor glycaemic control. In addition, favorable effects of a Ca 2+ ‐channel blocker on both [Ca 2+ ]i and RBC‐df have been demonstrated.