During hyperkalemia, aldosterone activates WNK, which stimulates ROMK-mediated K+ secretion by principal cells in the collecting duct. However, aldosterone does not directly stimulate NaCl reabsorption in the early distal tubule because it is not responsive to this hormone. In fact, the basal activity of WNK in the early distal tubule is low during hyperkalemia, resulting in decreased NaCl reabsorption via NCC. This decrease in NaCl reabsorption in the early distal tubule offsets the stimulatory effect of aldosterone, via SGK1, on ENaC-mediated Na+ reabsorption in principal cells of the collecting duct.

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) inhibit the reabsorption of NaCl and water. Increased extracellular fluid volume (ECFV) and increased myocardial wall pressure stimulate the secretion of ANP by the cardiac atria and BNP by the cardiac ventricles. These natriuretic peptides reduce blood pressure by decreasing total peripheral resistance and enhancing the urinary excretion of both NaCl and water. They achieve this primarily by increasing renal blood flow (RBF) and glomerular filtration rate (GFR). ANP and BNP vasodilate the afferent arterioles and vasoconstrict the efferent arterioles, resulting in increased GFR and filtration of NaCl, leading to increased NaCl excretion. Additionally, the increase in RBF reduces the concentration of NaCl in the medullary interstitium, thereby decreasing passive NaCl reabsorption by the thin ascending limb of Henle's loop.

ANP and BNP also inhibit NaCl reabsorption by the medullary portion of the collecting duct and AVP-stimulated water reabsorption across the collecting duct. Moreover, they reduce the secretion of AVP from the posterior pituitary. These actions are mediated by the activation of membrane-bound guanylyl cyclase receptors, which increase intracellular levels of cyclic guanine monophosphate (cGMP). ANP exhibits stronger natriuretic and diuretic effects compared to BNP.

Urodilatin, which shares a similar amino acid sequence with ANP, is encoded by the same gene. It is a 32-amino acid hormone that differs from ANP by the addition of four amino acids at the amino terminus. Urodilatin is secreted by the distal tubule and collecting duct and does not circulate systemically, thus influencing only kidney function. Its secretion is stimulated by an increase in blood pressure and ECFV. Urodilatin inhibits NaCl and water reabsorption across the medullary portion of the collecting duct. It is a more potent natriuretic and diuretic hormone than ANP due to the degradation of some ANP by a neutral endopeptidase, which does not affect urodilatin.
Fig. 34.10B . During hyperkalemia, aldosterone stimulates ROMK mediated K+ secretion by principal cells in the collecting duct by activating WNK. Because the early distal tubule is not directly responsive to aldosterone, this hormone does not stimulate NaCl reabsorption in this segment. In fact, because angiotensin II levels are not elevated by hyperkalemia, the basal activity of WNK in the early distal tubule is low, resulting in decreased NaCl reabsorption via NCC (see
Fig. 34.10B ). This effect of WNK on early distal tubule NaCl reabsorption offsets the stimulatory effect of aldosterone, via SGK1, on ENaC-mediated Na+ reabsorption in principal cells of the collecting duct.
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) inhibit NaCl and water reabsorption. Secretion of ANP by the cardiac atria and BNP by the cardiac ventricles are both stimulated by increased ECFV and increased myocardial wall pressure. ANP and BNP reduce blood pressure by decreasing total peripheral resistance and enhancing urinary excretion of both NaCl and water, primarily by increasing RBF and GFR. These natriuretic peptides vasodilate the afferent arterioles and vasoconstrict the efferent arterioles, which increases GFR and thus filtration of NaCl, thereby increasing NaCl excretion (see later discussion of glomerulotubular balance for the mechanism). In addition the increase in RBF decreases the concentration of NaCl in the medullary interstitium, which in turn reduces passive NaCl reabsorption by the thin ascending •Fig. 34.10 Aldosterone paradox (see text for details). +, stimulate; −, inhibit; AII, angiotensin II; NCC, NaCl symporter; ENaC, epithelial sodium channel; ROMK, K+ channel; WNK, with no lysine[K] kinases. There are four WNKs in the kidney; details are not given in the figure for clarity and because some of the details of WNK regulation of NCC, ENaC, and ROMK have not been elucidated.
limb of Henle’s loop (see earlier discussion for details on NaCl reabsorption by this segment). ANP and BNP also inhibit NaCl reabsorption by the medullary portion of the collecting duct and inhibit AVP-stimulated water reabsorption across the collecting duct. Moreover, ANP and BNP also reduce secretion of AVP from the posterior pituitary. These actions of ANP and BNP are mediated by the activation of membrane-bound guanylyl cyclase receptors, which increases intracellular levels of the second messenger cyclic guanine monophosphate (cGMP). ANP is a more profound natriuretic and diuretic agent than BNP.
Urodilatin and ANP are encoded by the same gene and have similar amino acid sequences. Urodilatin is a 32–amino acid hormone that differs from ANP by the addition of four amino acids to the amino terminus. Urodilatin is secreted by the distal tubule and collecting duct and is not present in the systemic circulation; thus urodilatin influences only the function of the kidneys. Secretion of urodilatin is stimulated by a rise in blood pressure and an increase in ECFV. It inhibits NaCl and water reabsorption across the medullary portion of the collecting duct. Urodilatin is a more potent natriuretic and diuretic hormone than ANP because some of the ANP that enters the kidneys in blood is degraded by a neutral endopeptidase that has no corresponding effect on urodilatin.