On the Pleotropic Actions of Mineralocorticoids

Abstract

Classical effects of mineralocorticoids include stimulation of Na⁺ reabsorption and K⁺ secretion in the kidney and other epithelia including colon and several glands. Moreover, mineralocorticoids enhance the excretion of Mg²⁺ and renal tubular H⁺ secretion. The renal salt retention following mineralocorticoid excess leads to extracellular volume expansion and hypertension. The increase of blood pressure following mineralocorticoid excess is, however, not only the result of volume expansion but may result from stiff endothelial cell syndrome impairing the release of vasodilating nitric oxide. Beyond that, mineralocorticoids are involved in the regulation of a wide variety of further functions, including cardiac fibrosis, platelet activation, neuronal function and survival, inflammation as well as vascular and tissue fibrosis and calcification. Those functions are briefly discussed in this short introduction to the special issue. Beyond that, further contributions of this special issue amplify on mineralocorticoid-induced sodium appetite and renal salt retention, the role of mineralocorticoids in the regulation of acid-base balance, the involvement of aldosterone and its receptors in major depression, the mineralocorticoid stimulation of inflammation and tissue fibrosis and the effect of aldosterone on osteoinductive signaling and vascular calcification. Clearly, still much is to be learned about the various ramifications of mineralocorticoid-sensitive physiology and pathophysiology.

Characteristics predicting clinical improvement and cure following laparoscopic adrenalectomy for primary aldosteronism in a large cohort

“…The resultant hypertension and hypokalemia classically seen in PA is, in part, because of this direct tubular effect. 23 In addition to sodium conservation and volume retention, hypertension is exacerbated by the secondary effects of hyperaldosteronism including progressive fibrosis in coronary and renal arterial vasculature, sympathetic autonomic excitation, and direct endothelial cell dysfunction. 9,24-27 Given these changes, patients with PA have been shown to be at an increased risk of cardiovascular mortality.…”

Aldosterone‐induced microRNAs act as feedback regulators of mineralocorticoid receptor signaling in kidney epithelia

“…This can be attributed in part to downregulation of the MR which occurs after binding to aldosterone. 19,78,79 The downregulation of MR occurs at the level of both protein and mRNA. 19 Negative feedback of MR reduces aldosterone signaling in cells and this is often observed in cultured cells as the ENaCmediated aldosterone response plateaus after an initial increase in the first 24 hours (see Figure 4C).…”

“…Cellular sensitivity to aldosterone is known to decrease with extended exposure. This can be attributed in part to downregulation of the MR which occurs after binding to aldosterone 19,78,79 . The downregulation of MR occurs at the level of both protein and mRNA 19 .…”

Harnessing the power of nutritional antioxidants against adrenal hormone imbalance-associated oxidative stress

“…Aldosterone raises blood pressure, affecting the heart. Mineralocorticoid receptors directly affect cardiac function, electrical conduction, OS, inflammation, and fibrosis, further harming the heart ( 68 ). Aldosterone/salt-induced hypertension in rats results in renal damage and an increase in the production of ROS in the renal cortex ( 69 ).…”