Low-Renin Hypertension in African Americans

描述(来自应用程序的逐字记录)：低肾素高血压很常见 在非裔美国人中，许多人未能达到正常血压 尽管有各种各样的降压药可用。这个 低肾素状态与钠的滞留增加相一致。我们有 黑人上皮钠的总体活性较高的证据 通道(ENaC)，肾脏内重吸收钠的主要部位 其中某些分子突变导致钠和严重的 低肾素高血压(利德尔综合征)。ENAC被醛固酮上调。 在目前的提案中，我们将研究两种抑制 ENAC活性，醛固酮的拮抗剂螺内酯和阿米洛利，a ENaC的直接抑制剂，在患有低肾素高血压的黑人中 对治疗产生抗药性。我们将遵循一个简单的协议，在该协议中我们将研究 服用最佳降压药物方案的患者，包括 服用全剂量利尿剂，但血压不正常的患者 已实现。患者将被随机分配到螺内酯25 mg/次。 每日，阿米洛利10毫克/天，螺内酯25毫克/天 阿米洛利每天10毫克，或安慰剂，疗程9周。在具体目标1中，我们将 测试耐药、低肾素高血压黑人的假设 通过小剂量的降压治疗使血压恢复正常 降低ENaC功能的药物。我们还将测试以下各项的协同效应 安体舒通联合阿米洛利降血压。在具体目标2中，我们 将检验这样一个假设，即抗ENaC药物降低 血压是通过降低ENaC功能的内在较高水平来实现的， 基线和更高水平的肾素和醛固酮水平较低证明了这一点 应答者在治疗过程中的增量。在具体目标#3中，我们将测试 假设螺内酯对血压的反应与 在ENaC亚基中存在分子变体，已经显示的变体 以前要与血压水平相关联。总而言之，我们探索 治疗黑人低肾素高血压的独特而简单的方法， 一种可能被证明对许多目前患有 血压失控。

DESCRIPTION (Verbatim from the application): Low-renin hypertension is common in African Americans, with many failing to achieve a normal blood pressure despite the availability of a wide variety of antihypertensive agents. The low-renin state is consistent with increased retention of sodium. We have evidence that blacks have higher overall activity of the epithelial sodium channel (ENaC), a principal site for reabsorption of sodium within the kidney and where certain molecular mutations result in retention of sodium and severe low-renin hypertension (Liddle's syndrome). ENaC is upregulated by aldosterone. In the present proposal, we will study the usefulness of two drugs that inhibit ENaC activity, spironolactone, an antagonist of aldosterone, and amiloride, a direct inhibitor of ENaC, in blacks with low-renin hypertension who have shown resistance to treatment. We will follow a simple protocol wherein we will study patients taking an optimal regimen of antihypertensive medication including a full dose of diuretic but in whom a normal blood pressure has not been achieved. The patients will be randomized to either spironolactone 25 mg per day, amiloride 10 mg per day, the combination of spironolactone 25 mg and amiloride 10 mg per day, or placebo for 9 weeks. In Specific Aim #1, we will test the hypothesis that drug-resistant, low-renin hypertensive blacks normalize their blood pressure in response to treatment with small doses of agents that reduce ENaC function. We will also test for a synergistic effect of spironolactone with amiloride to lower blood pressure. In Specific Aim #2, we will test the hypothesis that the mechanism whereby the anti-ENaC drugs lower blood pressure is by reducing an intrinsically higher level of ENaC function, as evidenced by lower levels of renin and aldosterone at baseline and greater increments during treatment in responders. In Specific Aim #3, we will test the hypothesis that blood pressure responses to spironolactone are related to the presence of molecular variants in ENaC subunits, variants that have been shown previously to associate with level of blood pressure. In summary, we explore unique but simple approaches to treatment of low-renin hypertension in blacks, a treatment modality that could prove useful to many patients currently with uncontrolled blood pressure.