Carter A R, Zhou Z H, Calhoun D A, Bubien J K
Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Am J Physiol Cell Physiol. 2001 Nov;281(5):C1413-21. doi: 10.1152/ajpcell.2001.281.5.C1413.
Pathophysiological features of both primary aldosteronism and pseudohyperaldosteronism are hyperactive amiloride-sensitive epithelial Na(+) channels (ENaC) and refractory hypertension. Peripheral blood lymphocytes express ENaC, which functions and is regulated similarly to ENaC expressed by renal principal cells. Thus it was hypothesized that individuals with either of these hypertensive etiologies could be identified by assessment of the function and regulation of peripheral blood lymphocyte ENaC, by whole cell patch clamp. We also tested the hypothesis that specific inhibition of hyperactive ENaC with amiloride could ameliorate the hypertension. To test these hypotheses, we solicited blood samples from normotensive, controlled hypertensive, and refractory hypertensive individuals. Lymphocytes were examined electrophysiologically to determine whether ENaC was hyperactive. All positive findings were from refractory hypertensive individuals. Nine refractory hypertensive patients had amiloride added to their hypertensive therapy. Amiloride normalized the blood pressure of four subjects. These individuals all had hyperactive ENaC. Amiloride had no effect on individuals with normal ENaC. These findings suggest that whole-cell patch clamp of peripheral blood lymphocytes can be used to identify accurately and rapidly hypertensive individuals who will respond to amiloride therapy.
原发性醛固酮增多症和假性醛固酮增多症的病理生理特征均为对氨氯地平敏感的上皮钠通道（ENaC）活性过高以及顽固性高血压。外周血淋巴细胞表达ENaC，其功能和调节与肾主细胞表达的ENaC相似。因此，有人提出假说，认为可通过全细胞膜片钳评估外周血淋巴细胞ENaC的功能和调节，来识别患有这两种高血压病因中任何一种的个体。我们还检验了用氨氯地平特异性抑制活性过高的ENaC可改善高血压的假说。为验证这些假说，我们采集了血压正常、血压得到控制的高血压患者以及顽固性高血压患者的血样。通过电生理检查淋巴细胞，以确定ENaC是否活性过高。所有阳性结果均来自顽固性高血压患者。9例顽固性高血压患者在其高血压治疗方案中加入了氨氯地平。氨氯地平使4名受试者的血压恢复正常。这些个体的ENaC均活性过高。氨氯地平对ENaC正常的个体没有影响。这些发现表明，外周血淋巴细胞全细胞膜片钳可用于准确、快速地识别对氨氯地平治疗有反应的高血压患者。
