Sodium chloride and aldosterone: harbingers of hypertension-related cardiovascular disease.
Sodium chloride and aldosterone: harbingers of hypertension-related cardiovascular disease.
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氯化钠和醛固酮：高血压相关心血管疾病的先兆。
DOI：
10.1161/hypertensionaha.109.136226
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kotchen,TheodoreA
中科院分区：
文献类型：
--
作者：
Kotchen,TheodoreA
饮食中的食盐摄入量和醛固酮都与高血压相关的心血管疾病的发病机制有关。动物、流行病学和临床研究表明，高盐摄入量与心肌肥厚有关，与血压无关。在体外，氯化钠直接诱导心肌和血管平滑肌细胞肥大。与高血压水平无关，氯化钠诱导的心肌肥厚可能是由一氧化氮合酶亚型介导的。1在大鼠中，限制饮食盐可防止血管紧张素II注射所致的氧化应激和心肌肥厚。临床上，在正常血压和高血压患者中，高盐摄入量与左心室重量增加有关。2在高血压患者中，高盐摄入量会放大靶器官损害的影响，包括左心室重量增加和微量白蛋白尿。在高血压患者中，氯化钠对左心室结构的影响可能通过血管紧张素II 2型受体基因的变异来调节。2醛固酮还与心肌结构和功能的改变有关。盐皮质激素受体存在于非上皮性组织(心脏、血管、脑)和上皮组织中，刺激这些受体可引起氧化应激，导致血管炎症、纤维化和心肌肥大。4此外，醛固酮可能通过增强血管紧张素II的促炎作用而导致终末器官损害。5在动物模型中，心脏负荷和循环中高水平的醛固酮都会刺激心肌内的纤维化，导致左心室肥厚。高血压病患者的血浆或尿醛固酮升高与左室构型的病理类型有关，原发性醛固酮增多症患者早期出现左室肥厚。对盐皮质激素拮抗剂的研究为醛固酮在心肌肥厚中的作用提供了令人信服的证据。动物和临床研究都证明，螺内酯或依普利酮可减少心肌肥厚和间质纤维化，与对血压的影响无关。6在实验模型中，醛固酮拮抗剂还可以预防肾肥大、肾小管间质纤维化、肾小球损伤、颈动脉硬化、阻力动脉重构和内皮功能障碍。5、7两项临床试验--随机心得安评估研究和依普利酮急性心肌梗死后心力衰竭疗效存活研究--显示，与服用安慰剂的患者相比，接受低剂量醛固酮拮抗剂治疗的心力衰竭患者的死亡率降低。8、9阻断盐皮质激素受体的有益作用至少部分归因于减轻盐皮质激素诱导的心肌氧化应激和冠状动脉炎症。值得注意的是，无论血浆浓度或尿醛固酮排泄量是否升高，盐皮质激素拮抗剂对心肌肥厚的有益影响都会发生。一种醛固酮合成酶抑制剂(FAD286)也被发现可以减轻单肾切除大鼠的心肌肥厚和间质纤维化，这些大鼠接受血管紧张素II治疗并喂食高盐饮食。5醛固酮的促炎作用被氯化钠放大，可能是通过增加氧化应激。在高盐摄入量的大鼠中，醛固酮刺激心脏、大血管和肾脏的纤维化。5氯化钠限制可防止氧化应激和…
Both dietary NaCl consumption and aldosterone have been implicated in the pathogenesis of hypertensionrelated cardiovascular disease. Animal, epidemiological, and clinical studies suggest that a high NaCl intake is associated with myocardial hypertrophy, independent of blood pressure. In vitro, NaCl directly induces hypertrophy in myocardial and vascular smooth muscle cells. Independent of the level of hypertension, NaCl induced cardiac hypertrophy may be mediated by nitric oxide synthase isoforms. 1 In the rat, dietary NaCl restriction prevents oxidative stress and cardiac hypertrophy induced by angiotensin II infusion. Clinically, a high NaCl intake is associated with increased left ventricular mass in both normotensive and hypertensive individuals. 2 In hypertensive patients, a high NaCl intake amplifies the effect of target organ damage, including increased left ventricular mass and microalbuminuria. Left ventricular mass decreases in response to dietary NaCl restriction, 3 and in hypertensive patients the effect of NaCl on left ventricular structure may be modulated by variants in the angiotensin II type 2 receptor gene. 2 Aldosterone is also associated with alterations of myocardial structure and function. Mineralocorticoid receptors are located in nonepithelial (heart, blood vessels, brain) as well as in epithelial tissues, and stimulation of these receptors may cause oxidative stress leading to vascular inflammation, fibrosis, and cardiac hypertrophy. 4 Additionally, aldosterone may contribute to end organ damage by enhancing the proinflammatory effects of angiotensin II. 5 In animal models, both cardiac load and high circulating aldosterone levels stimulate fibrosis within the myocardium, leading to left ventricular hypertrophy. Pathological patterns of left ventricular geometry have been associated with elevations of plasma or urine aldosterone in patients with essential hypertension, and the early onset of left ventricular hypertrophy has been described in patients with primary aldosteronism. Studies with mineralocorticoid antagonists provide convincing evidence for the contribution of aldosterone to cardiac hypertrophy. Both animal and clinical studies have documented that spironolactone or eplerenone decrease cardiac hypertrophy and interstitial fibrosis, independent of an effect on blood pressure. 6 In experimental models, aldosterone antagonists also protect against renal hypertrophy, tubulointerstitial fibrosis, glomerular injury, stiffening of the carotid artery, resistance artery remodeling, and endothelial dysfunction. 5, 7 Two clinical trials, the Randomized ALdactone Evaluation Study and the Eplerenone Postacute myocardial infarction Heart failure Efficacy Survival Study, demonstrated decreases in mortality in patients with heart failure treated with low doses of aldosterone antagonists compared to placebo-treated patients. 8, 9 The beneficial effects of mineralocorticoid receptor blockade have been attributed, at least in part, to attenuation of mineralocorticoid-induced myocardial oxidative stress and coronary vascular inflammation. Notably, the beneficial effects of mineralocorticoid antagonists on cardiac hypertrophy occur whether or not plasma concentrations or urine aldosterone excretion is elevated. An aldosterone synthase inhibitor (FAD286) has also been found to attenuate cardiac hypertrophy and interstitial fibrosis in uninephrectomized rats treated with angiotensin II and fed a high-salt diet. 5The proinflammatory effects of aldosterone are amplified by NaCl, possibly by increasing oxidative stress. In rats on a high NaCl intake, aldosterone stimulates fibrosis in the heart, great vessels, and kidney. 5 NaCl restriction prevents both oxidative stress …