Miller M A, Sagnella G A, Markandu N D, MacGregor G A
Blood Pressure Unit, St George's Hospital Medical School, London, UK.
J Hypertens. 1994 Aug;12(8):929-38.
To measure calcium,magnesium-ATPase (Ca-ATPase) activity and membrane fluidity in patients with essential hypertension compared with normotensive subjects; to investigate the interrelationship between membrane fluidity and the activity of the Ca-ATPase; and to assess the importance of circulating lipids on the Ca-ATPase and membrane fluidity.
Ca-ATPase and membrane fluidity were measured in erythrocyte membranes. Kinetic parameters [maximal activity (Vmax), apparent dissociation constant and allosteric number] of the Ca-ATPase activity were measured, in the presence of saturating calmodulin, in 38 normotensives and 57 essential hypertensives. Fluorescent polarization anisotropy, as an index of membrane fluidity, was measured, using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium DPH (TMA-DPH) in 37 normotensives and 44 hypertensives. Of these 22 were paired for age, sex and race.
There was no significant difference in the Vmax and allosteric number of the Ca-ATPase between the normotensives and hypertensives, but there was a trend for the hypertensives to have a reduced calcium affinity. In contrast, hypertensive subjects had significantly lower membrane fluidity. Sex and serum triglycerides level were important determinants of membrane fluidity in both groups. Comparisons between normotensives and hypertensives demonstrated decreased fluidity in the hypertensives independent of sex and serum triglycerides level, although the differences, especially with TMA-DPH, were more pronounced in the females. In both groups there were negative correlations between Vmax and both DPH and TMA-DPH anisotropy.
The present study demonstrates that essential hypertension is associated with a generalized alteration in the erythrocyte membrane physical and chemical properties. However, despite the positive correlation between Vmax and membrane fluidity, the present study also demonstrates that essential hypertension is not associated with a major abnormality in the activity of the erythrocyte Ca-ATPase in isolated membranes.
测量原发性高血压患者与血压正常者红细胞膜上钙、镁 -ATP 酶(Ca -ATP 酶)活性及膜流动性;研究膜流动性与 Ca -ATP 酶活性之间的相互关系;评估循环脂质对 Ca -ATP 酶和膜流动性的重要性。
测定红细胞膜中的 Ca -ATP 酶和膜流动性。在 38 名血压正常者和 57 名原发性高血压患者中,于饱和钙调蛋白存在的情况下,测定 Ca -ATP 酶活性的动力学参数[最大活性(Vmax)、表观解离常数和别构数]。使用荧光探针 1,6 -二苯基 -1,3,5 -己三烯(DPH)和三甲基铵 DPH(TMA -DPH),在 37 名血压正常者和 44 名高血压患者中测量作为膜流动性指标的荧光偏振各向异性。其中 22 对在年龄、性别和种族方面进行了匹配。
血压正常者和高血压患者之间 Ca -ATP 酶的 Vmax 和别构数无显著差异,但高血压患者的钙亲和力有降低趋势。相比之下,高血压患者的膜流动性显著较低。性别和血清甘油三酯水平是两组膜流动性的重要决定因素。血压正常者与高血压患者的比较表明,高血压患者的膜流动性降低,且与性别和血清甘油三酯水平无关,尽管差异(尤其是使用 TMA -DPH 时)在女性中更为明显。在两组中,Vmax 与 DPH 和 TMA -DPH 各向异性均呈负相关。
本研究表明原发性高血压与红细胞膜理化性质的普遍改变有关。然而,尽管 Vmax 与膜流动性呈正相关,但本研究也表明原发性高血压与离体膜中红细胞 Ca -ATP 酶活性的主要异常无关。