Sagnella G A, Miller M A, Khong T K, MacGregor G A
Blood Pressure Unit, St George's Hospital Medical School, London, UK.
Clin Chim Acta. 1999 May;283(1-2):105-18. doi: 10.1016/s0009-8981(99)00041-8.
Increased activity of sodium/hydrogen exchange provides a potentially important mechanism for the development of hypertension. The aims of this study were to compare platelet sodium/hydrogen exchanger activity and renal acid-base excretion in normotensives and hypertensives of Caucasian origin. Platelet intracellular pH (pHi) was measured using the fluorescent dye BCECF to monitor intracellular pH. Sodium/hydrogen exchanger activity was estimated from the recovery of pHi clamped to 6.25 with nigericin. Normotensives had supine blood pressures of < 140 and < 90 mmHg; those with essential hypertension had blood pressures > 150/95 mmHg with no known secondary cause. Measurements of platelet pHi and sodium/hydrogen exchanger activity were made on 26 normotensives (ten female, sixteen male) and 25 hypertensives (five female, twenty male). All subjects were on their usual dietary sodium intake. Statistical analysis was by two-way analysis of variance for gender and blood pressure status. Group values are expressed as means+/-SD and a P value of < 0.05 was taken as being statistically significant. There were no significant differences in platelet pHi between the normotensive (n = 26) and the hypertensive (n = 25) group: pHi 7.21+/-0.14 and 7.18+/-0.16, respectively. The pHi recovery after acidification was sodium-dependent and inhibited by N-hexamethylene amiloride. Comparison of kinetic constants showed no significant differences between the normotensive and the hypertensive groups: values for rate constants and initial velocities were 0.24+/-0.04 s(-1), 0.16+/-0.03 dpHi/s for the normotensives and 0.25+/-0.05 s(-1), 0.16+/-0.03 dpHi/s for the hypertensives, respectively; there were also no significant differences in proton fluxes. The inability to find raised platelet sodium/hydrogen exchanger in the hypertensives contrasts with previous observations using other methods for the measurement of this exchanger in platelets and this raises important methodological issues in the assessment of platelet sodium/hydrogen exchanger activity.
钠/氢交换活性增加为高血压的发生提供了一种潜在的重要机制。本研究的目的是比较白种人正常血压者和高血压者的血小板钠/氢交换活性及肾脏酸碱排泄情况。使用荧光染料羧基-SNARF-1监测细胞内pH值,测量血小板细胞内pH(pHi)。用尼日利亚菌素将pHi钳制在6.25后,根据其恢复情况估算钠/氢交换活性。正常血压者仰卧位血压<140/90 mmHg;原发性高血压患者血压>150/95 mmHg,且无已知的继发性病因。对26名正常血压者(10名女性,16名男性)和25名高血压者(5名女性,20名男性)进行了血小板pHi和钠/氢交换活性测量。所有受试者均按其平常的饮食钠摄入量进食。采用双向方差分析对性别和血压状态进行统计分析。组值以均值±标准差表示,P值<0.05被视为具有统计学意义。正常血压组(n = 26)和高血压组(n = 25)的血小板pHi无显著差异:分别为7.21±0.14和7.18±0.16。酸化后pHi的恢复依赖于钠,并被N-六亚甲基阿米洛利抑制。动力学常数比较显示,正常血压组和高血压组之间无显著差异:正常血压者的速率常数和初始速度值分别为0.24±0.04 s⁻¹、0.16±0.03 dpHi/s,高血压者分别为0.25±0.05 s⁻¹、0.16±0.03 dpHi/s;质子通量也无显著差异。在高血压患者中未能发现血小板钠/氢交换增加,这与之前使用其他方法测量血小板中该交换体的观察结果形成对比,这在评估血小板钠/氢交换活性方面提出了重要的方法学问题。