期刊
AMERICAN JOURNAL OF HYPERTENSION
卷 20, 期 1, 页码 109-117出版社
OXFORD UNIV PRESS
DOI: 10.1016/j.amjhyper.2006.05.022
关键词
hypertension; cardiovascular disease; epithelial sodium channel; amiloride
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [F32HL080872] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K24DK002818, T32DK007257] Funding Source: NIH RePORTER
- NHLBI NIH HHS [F32 HL 80872-01] Funding Source: Medline
- NIDDK NIH HHS [5T32 DK 007257-25, 5K24 DK 02818-02] Funding Source: Medline
Amiloride was originally described in 1967 as a potassium-sparing diuretic, the mechanism of action of which is to block the epithelial sodium channel (ENaC) within the distal tubule of the kidney. In addition, higher doses of amiloride were found to be capable of inhibiting the Na+/H+ exchangers (NHE) and the Na+/Ca+ exchangers. In time, several amiloride analogs have been synthesized to have a marked increase in their specificity to inhibit the ENaC, the NHE or the Na+/Ca+ exchangers. Although the NHE inhibitors have received the most recent attention, large-scale clinical trials using NHE inhibitors in ischemic cardiac states have shown them to be either ineffective or associated with an unacceptable risk profile. Aldosterone excess in animal models is known to cause cardiovascular injury, and blockade of mineralocorticoid receptors in human beings with heart disease improves outcomes. However, the exact mechanisms of aldosterone injury in animal models of hypertensive disease and protection with mineralocorticoid receptor antagonists in human trials of heart failure remain unknown. These effects are unexplained by changes in BP, potassium, or sodium balance. An additional possibility is that aldosterone action and mineralocorticoid receptor blockade is conferred by alterations in ENaC activity. Emerging experimental evidence suggests the possibility that systemic or central ENaC inhibition or both may be an alternative to the treatment of hypertension and cardiovascular disease states. Clinical trials to evaluate further the potential beneficial cardiovascular effects of ENaC blockade are needed. This article reviews the case for ENaC inhibition as a potential target for cardiovascular and renal protection in human beings.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据