Tsuda K, Minatogawa Y, Furuya S, Ueda E, Kusuyama Y, Shima H, Tamaki T, Nishio I, Kido R, Masuyama Y
Jpn Circ J. 1986 Nov;50(11):1158-64. doi: 10.1253/jcj.50.1158.
To investigate the Ca-sensitivity of the erythrocyte membrane in hypertension, the changes of the osmotic fragility of erythrocytes by Ca-loading and the effects of Ca-channel blockers or calmodulin-antagonist were observed in patients with essential hypertension. Erythrocytes were obtained from untreated patients with essential hypertension and age-matched normotensive subjects. Treatment of erythrocytes with Ca-ionophore A23187 and Ca in bathing medium caused the reduction of the osmotic fragility of erythrocytes dose-dependently on Ca-concentration. The degree in alteration of the osmotic fragility of erythrocytes was greater in essential hypertension than that in normotensive controls. In addition, Ca-induced changes of erythrocyte osmotic fragility was inversely correlated with the plasma renin activity in essential hypertension. In the presence of Ca-antagonists (verapamil, diltiazem) or calmodulin-antagonist (trifluoperazine), the reduction of the osmotic fragility of erythrocytes by Ca-loading was inhibited, and the differences of the osmotic fragility of erythrocytes between the hypertensives and the normotensive controls were abolished by these drugs. These results suggest that the greater changes of the osmotic fragility of the erythrocytes by Ca-loading in essential hypertension might be due to the abnormality of Ca-handling of the cell membranes causing an increase in the intracellular Ca concentration, contributing at least partially to the pathogenesis of hypertension.
为研究高血压患者红细胞膜的钙敏感性,观察了原发性高血压患者经钙负荷后红细胞渗透脆性的变化以及钙通道阻滞剂或钙调蛋白拮抗剂的作用。红细胞取自未经治疗的原发性高血压患者和年龄匹配的血压正常者。用钙离子载体A23187和培养基中的钙处理红细胞,可使红细胞的渗透脆性随钙浓度呈剂量依赖性降低。原发性高血压患者红细胞渗透脆性的改变程度大于血压正常对照组。此外,在原发性高血压中,钙诱导的红细胞渗透脆性变化与血浆肾素活性呈负相关。在存在钙拮抗剂(维拉帕米、地尔硫䓬)或钙调蛋白拮抗剂(三氟拉嗪)的情况下,钙负荷导致的红细胞渗透脆性降低受到抑制,并且这些药物消除了高血压患者和血压正常对照组之间红细胞渗透脆性的差异。这些结果表明,原发性高血压患者经钙负荷后红细胞渗透脆性的较大变化可能是由于细胞膜钙处理异常导致细胞内钙浓度升高,这至少部分促成了高血压的发病机制。