Signaling mechanisms that link salt retention to hypertension: Endogenous ouabain, the Na+ pump, the Na+/Ca2+ exchanger and TRPC proteins

被引:51
作者
Blaustein, Mordecai P. [1 ,2 ]
Hamlyn, John M. [3 ]
机构
[1] Univ Maryland, Sch Med, Dept Physiol, 655 W Baltimore St, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Ctr Heart Hypertens & Kidney Dis, Baltimore, MD 21201 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2010年 / 1802卷 / 12期
基金
美国国家卫生研究院;
关键词
Salt-dependent hypertension; Calcium; Sodium pump; Sodium/calcium exchanger; Receptor-operated channel; DEPENDENT ENERGY-UTILIZATION; NA; K-ATPASE ALPHA-2 ISOFORM; ARTERIAL SMOOTH-MUSCLE; BLOOD-PRESSURE; K-ATPASE; CARDIAC-GLYCOSIDES; SODIUM-PUMP; ANTIHYPERTENSIVE COMPOUND; SENSITIVE HYPERTENSION; CARDIOTONIC STEROIDS;
D O I
10.1016/j.bbadis.2010.02.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Salt retention as a result of chronic, excessive dietary salt intake, is widely accepted as one of the most common causes of hypertension. In a small minority of cases, enhanced Na+ reabsorption by the kidney can be traced to specific genetic defects of salt transport, or pathological conditions of the kidney, adrenal cortex, or pituitary. Far more frequently, however, salt retention may be the result of minor renal injury or small genetic variation in renal salt transport mechanisms. How salt retention actually leads to the increase in peripheral vascular resistance (the hallmark of hypertension) and the elevation of blood pressure remains an enigma. Here we review the evidence that endogenous ouabain (an adrenocortical hormone), arterial smooth muscle alpha 2 Na+ pumps, type-1 Na/Ca exchangers, and receptor- and store-operated Ca2+ channels play key roles in the pathway that links salt to hypertension. We discuss cardenolide structure-function relationships in an effort to understand why prolonged administration of ouabain, but not digoxin, induces hypertension, and why digoxin is actually anti-hypertensive. Finally, we summarize recent observations which indicate that ouabain upregulates arterial myocyte Ca2+ signaling mechanisms that promote vasoconstriction, while simultaneously downregulating endothelial vasodilator mechanisms. In sum, the reports reviewed here provide novel insight into the molecular mechanisms by which salt retention leads to hypertension. (c) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:1219 / 1229
页数:11
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