Aldosterone Receptors and Effector Mechanisms in Mononuclear Leukocytes in Different Forms of Hypertension

Abstract

One of the most important factors which regulate electrolytes, blood volume, and blood pressure is aldosterone. Mineralocorticoids by definition affect mineral metabolism, and probably all the factors related to hypertension usually studied at the cellular level are directly or indirectly influenced by the action of this hormone (sodium, calcium, electrolyte exchange systems, etc). The aim of the present study was to evaluate mineralocorticoid effector mechanisms in different types of hypertension. A change in plasma or urine content of aldosterone is not always an indicator of increased effect as demonstrated for example in pseudohypoaldosteronism. To have an effect aldosterone must act at the level of target tissues, and its effect is mediated by binding to mineralocorticoid receptors (type I corticosteroid receptors). The type I receptor shows high and equivalent affinity for aldosterone, deoxycorticosterone, and corticosterone. From these data it is difficult to explain why these receptors respond to aldosterone, since the plasma concentration of glucocorticoids is much higher and one would expect these receptors to be occupied by glucocorticoids. In vivo, however, the classical target tissues for aldosterone are highly specific for this hormone, probably as a consequence of intracellular specificity-conferring mechanisms. Some such mechanisms have been postulated or evaluated: presence in the tissue or in the cells of corticosteroid-binding globulin (CBG) [1], or a different intracellular metabolism of glucocorticoids (11-hydroxysteroid dehydrogenase and oxoreductase system and 5α-and 5β-reductase). These mechanisms would allow aldosterone to bind to its receptors by reducing the availability of free glucocorticoids in the cell. In other clinical situations it seems that cortisol binds to mineralocorticoid receptors, leading to a mineralocorticoid response. In this case reduction of 11-hydroxysteroid dehydrogenase increases the concentration of free cortisol in the cells and the subsequent binding of the steroid to type I receptors [2,3].

Partly supported by Nato grant 07 07 87.