Salt and Aldosterone

Abstract

A very large number of experimental and human studies independently link high dietary salt intake and aldosterone excess to the development and progression of end-organ damage. Observational and dietary interventional studies clearly establish high diet salt intake as an important contributor to the development of hypertension, cardiac hypertrophy, and proteinuria. Likewise, observational data and studies of aldosterone blockade demonstrate that hyperaldosteronism significantly relates to level of blood pressure, intracardiac volumes, left ventricular mass, and urinary protein excretion. As such, these studies establish both high dietary salt intake and excess aldosterone to be important and independent mediators of cardiovascular risk. 1,2 It is interesting, however, that animal models of hyperaldosteronism have consistently demonstrated that the unfavorable target-organ effects of aldosterone are in fact dependent on the concomitant dietary sodium intake. Beginning with landmark studies by Brilla and Weber, 3 it has been repeatedly demonstrated that the proinflammatory and profibrotic effects of excess aldosterone induced in end organs, including the heart, vasculature, and kidney, do not manifest unless the dietary salt intake is also excessive. 4,5 That is, the deleterious tissue effects of aldosterone could be largely avoided by maintaining the rats on a low-salt diet.Until recently, such an interaction between sodium and aldosterone in humans, while anticipated, had not been clearly observed. Now, however, a growing body of data, including the article by du Cailar et al 6 in this edition of Hypertension, demonstrates that the blood pressure and target-organ effects of excess aldosterone and excess dietary sodium are in large part dependent on each other. That is, as had been predicted by animal models of excess aldosterone, endogenous aldosterone and dietary sodium consumption in hypertensive patients do not contribute in solo but instead act in concert to accelerate target-organ decline.Aldosterone, Dietary Sodium, and Target-Organ Damage du Cailar et al 6 measured plasma aldosterone levels, 24-hour urinary sodium excretion, and left ventricular mass index in 182 never-treated patients with primary hypertension. The patients were then treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor antagonist, with other agents added as needed for blood pressure control. After 3 years of treatment, the biochemical and echocardiographic assessments were repeated. In response to treatment, the reduction in left ventricular mass index was positively correlated with changes in systolic blood pressure, urinary sodium excretion, and plasma aldosterone. At the end of the treatment period, when the cohort was compared by tertiles of urinary sodium excretion and high or low aldosterone levels (ie, above or below the median), it was found that left ventricular mass index increased progressively in relation to increasing urinary sodium excretion in the high-aldosterone subjects. No such relation, h...

Aldosterone effects on glomerular structure and function

“…Several works have in fact demonstrated that salt and aldosterone synergistically contribute to renal impairment. 14–16 Moreover, to discriminate the contribution of salt to glomerulosclerosis development, we randomized the rats to either salt or aldosterone, or both. Based on these premises, 75 wild-type male Wistar rats, weighing 250 g, underwent left uninephrectomy at baseline and were randomized to 5 different groups one week after.…”

A Single Initiating Cause of Hypertension; Potential for Primary Prevention

“…It has been amply demonstrated that aldosterone in the presence of high salt diet leads to cardiovascular [83] and renal damage [84] in patients with hypertension, and that low salt diet is capable of reversing these effects [83][84][85]. The mechanisms underlying this important observation of fundamental relevance have not been adequately explained.…”

“…It is recognized that salt and aldosterone act in concert to produce a combined effect on target organ damage [83,85]. High salt intake requires elevated aldosterone to produce target organ damage and conversely low salt intake requires aldosterone to be normal for the full expression of its salutary effects.…”

Translational Success Stories: Angiotensin Receptor 1 Antagonists in Heart Failure

“…184 There is now evidence in patients with hypertension that high dietary salt is also necessary for adverse myocardial effects manifested by LV hypertrophy. 185,186 In a recent crosssectional study conducted in patients with resistant hypertension, aldosterone excess and high dietary salt combined to sustain excessive urinary protein excretion, 187 and salt restriction alone resulted in significant decreases in blood pressure in patients with resistant hypertension and hyperaldosteronism. 188 Such studies generated a concept of "salt-aldosterone product" in the aldosterone-mediated inflammation that impairs both kidney and cardiac function.…”