stimulation of AVP secretion and thirst 4.
enhancement of NaCl reabsorption by the proximal tubule, thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct (Of these segments the effect on the proximal tubule is quantitatively the largest.) Angiotensin II is an important secretagogue for aldoste rone. An increase in plasma K+ concentration is the other important stimulus for aldosterone secretion (see ). Aldosterone is a steroid hormone produced by the glomerulosa cells of the adrenal cortex and acts in a number of ways on the kidneys (see also
Chapters 34, 36, and ). With regard to regulation of the ECFV, aldosterone reduces NaCl excretion by stimulating its reabsorption by several nephron segments. Most importantly it stimulates NaCl reabsorption in the aldosterone-sensitive distal nephron (ASDN), which consists of the latter portion of the distal tubule and the collecting duct. To a lesser extent it also stimulates NaCl reabsorption by the thick ascending limb of Henle’s loop and the early portion of the distal tubule.
Aldosterone sensitivity is conferred by the presence of mineralocorticoid receptors as well as the enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). Because the mineralocorticoid receptor also binds glucocorticoids, 11β-HSD2 is required for aldosterone specificity because it metabolizes glucocorticoids and thus prevents them from binding to the mineralocorticoid receptor. The aldosterone-sensitive distal nephron expresses both the mineralocorticoid receptor and 11β-HSD2.
). In the ASDN it increases the abundance and activity of ENaC in the apical membrane of principal cells. This increases Na+ entry into cells across the apical membrane. Extrusion of Na+ from cells across the basolateral membrane occurs by Na+,K+-ATPase, the abundance of which is also increased by aldosterone. Thus aldosterone increases reabsorption of NaCl from the tubular fluid by distal nephron segments, whereas reduced levels of aldosterone decreases the amount of NaCl reabsorbed by these segments. Although the principal site of action of aldosterone is the ASDN, aldosterone also increases the abundance of the Na+/Cl− symporter in the distal tubule and the Na+/K+/2Cl− symporter in the thick ascending limb of Henle’s loop.
Box 35.1 , activation of the RAAS, as occurs with ECFV depletion, decreases excretion of NaCl
Diseases of the adrenal cortex can alter aldosterone levels and thereby impair the ability of the kidneys to maintain Na+ balance and euvolemia. With decreased secretion of aldosterone (hypoaldosteronism), the reabsorption of NaCl, mainly by the aldosterone-sensitive distal nephron, is reduced and NaCl is lost in the urine. Because urinary NaCl loss can exceed the amount of NaCl ingested in the diet, negative Na+ balance ensues and ECFV decreases. In response to ECFV contraction, sympathetic tone is increased and levels of renin, angiotensin II, and AVP are elevated. With increased aldosterone secretion (hyperaldosteronism) the effects are the opposite; NaCl reabsorption by the aldosterone-sensitive distal nephron is enhanced and excretion of NaCl is reduced. Consequently, ECFV is increased, sympathetic tone is decreased, and levels of renin, angiotensin II, and AVP are decreased. As described later, ANP and BNP levels are also elevated in this setting.
by the kidneys. The RAAS is suppressed with ECFV expansion, and renal NaCl excretion is therefore enhanced.