Warnock D G
Department of Medicine, University of Alabama at Birmingham, 35294-0007, USA.
Semin Nephrol. 2000 Jan;20(1):40-6.
With the expression cloning of the subunits of the epithelial sodium channel, a new era has evolved in our basic understanding of the low-renin forms of human hypertension. The monogenic hypertensive syndromes manifest dysregulation of the epithelial sodium channel in the cortical collecting tubule. These rare syndromes provide a schema for organizing our thinking about the more common form(s) of low renin hypertension, and raise the possibility that dysregulation of sodium channel activity and consequent salt retention and volume expansion provide a basic pathophysiological mechanism for low-renin hypertension. What are needed are more specific agents to interrupt the mineralocorticoid response pathways, and clinically relevant approaches to measuring sodium channel activity at the level of the collecting tubule in the individual patient. The combined use of aldosterone antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists could have a beneficial effect on "progression" of renal disease associated with glomerular and interstitial fibrosis, especially if the effects of hyperkalemia on the heart and aldosterone secretion can be minimized.
随着上皮钠通道亚基的表达克隆，我们对人类低肾素型高血压的基本认识进入了一个新时代。单基因高血压综合征表现为皮质集合管上皮钠通道调节异常。这些罕见综合征为我们思考更常见的低肾素高血压形式提供了一个框架，并增加了钠通道活性调节异常以及随之而来的盐潴留和容量扩张是低肾素高血压基本病理生理机制的可能性。我们需要的是更具特异性的药物来阻断盐皮质激素反应途径，以及在个体患者的集合管水平测量钠通道活性的临床相关方法。醛固酮拮抗剂与血管紧张素转换酶抑制剂或血管紧张素受体拮抗剂联合使用可能对与肾小球和间质纤维化相关的肾脏疾病“进展”产生有益影响，特别是如果高钾血症对心脏和醛固酮分泌的影响能够降至最低。
