The isosmotic reabsorption of NaCl and water in the proximal tubule is greatly influenced by Angiotensin II, as well as other hormones like dopamine and adrenomedullin. Glomerulotubular balance and Starling forces also play a role in NaCl reabsorption. The direct regulation of water excretion by the kidneys is primarily done by AVP.

When the extracellular fluid volume (ECFV) decreases, the renin-angiotensin-aldosterone system is activated, leading to an increase in the plasma concentration of angiotensin II. Angiotensin II then stimulates the reabsorption of NaCl and Na+ in various segments of the nephron, including the thick ascending limb of Henle's loop, late distal tubule, and collecting duct.

Aldosterone, which is synthesized by the glomerulosa cells of the adrenal cortex, plays a significant role in NaCl reabsorption. It primarily acts on the late distal tubule and collecting duct, enhancing the reabsorption of NaCl through different mechanisms. These mechanisms include increasing the amount of Na+,K+-ATPase in the basolateral membrane, increasing the expression of the sodium channel (ENaC) in the apical cell membrane, elevating Sgk1 levels, and stimulating CAP1, a serine protease that activates ENaCs.

The increase in Na+ reabsorption results in a negative transepithelial luminal voltage across the late distal tubule and collecting duct, facilitating the reabsorption of Cl− across the tight junctions. Aldosterone also stimulates the secretion of K+ by the late distal tubule and collecting duct.

Other factors that influence NaCl and water reabsorption include ANP, BNP, and urodilatin, which increase extracellular fluid volume and decrease the reabsorption of H2O and NaCl. Uroguanylin and guanylin, when ingested orally, decrease the reabsorption of H2O and NaCl. Sympathetic nerves also play a role in NaCl and water reabsorption, with a decrease in extracellular fluid volume leading to an increase in reabsorption in various segments of the nephron.
Table 34.6).
However, other hormones (including dopamine and adrenomedullin), Starling forces, and the phenomenon of glomerulotubular balance also influence NaCl reabsorption. AVP is the only major hormone that directly regulates the amount of water excreted by the kidneys.
Angiotensin II has a potent stimulatory effect on the isosmotic reabsorption of NaCl and water in the proximal tubule. It also stimulates reabsorption of Na+ in the thick ascending limb of Henle’s loop, as well as the late distal tubule and collecting duct. A decrease in ECFV activates the renin-angiotensin-aldosterone system (see for more details), thereby increasing the plasma concentration of angiotensin II.
Aldosterone is synthesized by the glomerulosa cells of the adrenal cortex and stimulates reabsorption of NaCl by the thick ascending limb of Henle’s loop, the late distal tubule, and the collecting duct. Most of aldosterone’s effect on NaCl reabsorption reflects its action on the late distal tubule and collecting duct. Aldosterone enhances reabsorption of NaCl across principal cells in these segments by four mechanisms: (1) increasing the amount of Na+,K+-ATPase in the basolateral membrane; (2) increasing expression of the sodium channel (ENaC) in the apical cell membrane; (3) elevating Sgk1 (serum glucocorticoid-stimulated kinase; see the molecular box) levels, which also increases the expression of ENaC in the apical cell membrane; and (4) stimulating •Fig. 34.9 Transport pathways in principal cells, α-intercalated cells, and β-intercalated cells of the late segment of the distal tubule and collecting duct. CA, carbonic anhydrase. Principal cells reabsorb Na+and secrete K+. K+is secreted by two types of K+channels (ROMK and BK) and by a K+/Cl−symporter (KCC1). α-Intercalated cells secrete H+and reabsorb HCO3−and K+, and β-intercalated cells secrete HCO3−and reabsorb H+and Cl−. CO2 + H2O HCO− 3 CA Cl− Cl− H+ ˙-Intercalated cell Pendrin V-ATPase Blood
CAP1 (channel-activating protease, also called prostatin), a serine protease that directly activates ENaCs by proteolysis. Taken together, these actions increase Na+ uptake across the apical cell membrane and facilitate Na+ exit from the cell interior into blood. The increase in reabsorption of Na+ generates a negative transepithelial luminal voltage across the late distal tubule and the collecting duct. This negative voltage in the lumen provides the electrochemical driving force for reabsorption of Cl− across the tight junctions. Aldosterone also stimulates secretion of K+ by the late distal tubule and collecting duct (collectively referred to as the aldosterone-sensitive distal nephron (ASDN)
Angiotensin II↑ReninPT, TAL, DT/CD↑NaCl and H2O reabsorptionAldosterone↑Angiotensin II, ↑[K+]pTAL, DT/CD↑NaCl and H2O reabsorption
ANP, BNP, urodilatin↑ECFVCD↓H2O and NaCl reabsorptionUroguanylin, guanylinOral ingestion of NaClPT, CD↓H2O and NaCl reabsorptionSympathetic nerves↓ECFVPT, TAL, DT/CD↑NaCl and H2O reabsorption