Rivera A, Conlin P R, Williams G H, Canessa M L
Department of Medicine, Brigham and Women's Hospital, Boston, Mass. 02115, USA.
Hypertension. 1996 Aug;28(2):213-8. doi: 10.1161/01.hyp.28.2.213.
Abnormalities of intracellular calcium homeostasis and sodium-proton exchange have been implicated in the pathophysiology of essential hypertension. To further define the nature of cytosolic calcium abnormalities and whether they relate to increased sodium-proton exchange in hypertension, we have studied peripheral lymphocytes from normotensive and hypertensive subjects. Lymphocyte cytosolic calcium was significantly increased (P < .01) in hypertensive compared with normotensive subjects while consuming a high salt diet. Using maximum likelihood analysis, we found that cytosolic calcium levels in our study population were not normally distributed and observed three modes (P < .02). The means of the first mode and the two upper modes were separated (+/-2 SD) at a cytosolic calcium level of 120 nmol/L. We conducted further analysis in the subgroups with cytosolic calcium levels > 120 nmol/L or < 120 nmol/L. The majority of the normotensive subjects (86%) and half of the hypertensive subjects (52%) had levels < 120 nmol/L. Clinical characteristics of the two subgroups did not differ. Subjects with levels < 120 nmol/L had a rise in cytosolic calcium when changed to a low salt diet; those with levels > 120 nmol/L did not show a change in cytosolic calcium but their blood pressure fell significantly with salt restriction. Hypertensive subjects also had increased sodium-proton exchange activity compared with normotensive subjects when both groups were studied in a high salt balance. A positive correlation between sodium-proton exchange and cytosolic calcium was observed in subjects with levels < 120 nmol/L. There was insufficient power to draw conclusions on this relationship in subjects with levels > 120 nmol/L. Thus, many hypertensive subjects have increased cytosolic calcium, but this abnormality is not associated with sodium-proton exchange activity in all individuals. The salt-induced change in cytosolic calcium in subjects with levels < 120 nmol/L and its link to sodium-proton exchange suggest regulation by factors involved in salt-volume homeostasis. Individuals with cytosolic calcium > 120 nmol/L, most of whom were hypertensive, may have abnormalities in this regulation, contributing to hypertension.
细胞内钙稳态异常和钠-质子交换与原发性高血压的病理生理学有关。为了进一步明确细胞溶质钙异常的性质以及它们是否与高血压中钠-质子交换增加有关，我们研究了正常血压和高血压受试者的外周淋巴细胞。与正常血压受试者相比，高血压受试者在摄入高盐饮食时淋巴细胞细胞溶质钙显著增加（P <.01）。使用最大似然分析，我们发现研究人群中的细胞溶质钙水平呈非正态分布，并观察到三种模式（P <.02）。第一种模式与两种较高模式的均值在细胞溶质钙水平为120 nmol/L时分开（±2 SD）。我们对细胞溶质钙水平> 120 nmol/L或< 120 nmol/L的亚组进行了进一步分析。大多数正常血压受试者（86%）和一半的高血压受试者（52%）的水平< 120 nmol/L。两个亚组的临床特征没有差异。细胞溶质钙水平< 120 nmol/L的受试者改为低盐饮食时细胞溶质钙升高；水平> 120 nmol/L的受试者细胞溶质钙没有变化，但他们的血压随着盐限制而显著下降。在高盐平衡状态下研究时，高血压受试者与正常血压受试者相比钠-质子交换活性也增加。在细胞溶质钙水平< 120 nmol/L的受试者中观察到钠-质子交换与细胞溶质钙之间呈正相关。对于细胞溶质钙水平> 120 nmol/L的受试者，没有足够的能力就这种关系得出结论。因此，许多高血压受试者细胞溶质钙增加，但这种异常并非在所有个体中都与钠-质子交换活性相关。细胞溶质钙水平< 120 nmol/L的受试者中盐诱导的细胞溶质钙变化及其与钠-质子交换的联系表明受盐-容量稳态相关因素的调节。细胞溶质钙> 120 nmol/L的个体，其中大多数是高血压患者，可能在这种调节中存在异常，导致高血压。
