Cellular mechanisms and regulation of sodium chloride (NaCl) and volume reabsorption along the proximal tubule. The sodium-potassium adenosine triphosphate (Na-K ATPase) pump (shown as white circle with light blue outline) at the basolateral cell membrane keeps the intracellular Na concentration low; the K concentration high; and the cell membrane voltage oriented with the cell interior negative, relative to the exterior. Many pathways participate in Na entry across the luminal membrane. Only the sodium-hydrogen (Na-H) exchanger is shown because its regulation in states of volume excess and depletion has been characterized extensively. Activity of the Na-H exchanger is increased by stimulation of renal nerves, acting by way of a receptors and by increased levels of circulating angiotensin II (AII), as shown in Figures 2-7 and 2-13 [25-28]. Increased levels of dopamine (DA1) act to inhibit activity of the Na-H exchanger [29,30]. Dopamine also acts to inhibit activity of the Na-K ATPase pump at the basolateral cell membrane . As described in Figure 2-14, increases in the filtration fraction (FF) lead to increases in oncotic pressure (wonc) in per-itubular capillaries and decreases in peritubular and interstitial hydrostatic pressure (Pi). These changes increase solute and volume absorption and decrease solute backflux. Water flows through water channels (Aquaporin-1) Na and Cl also traverse the paracel-lular pathway.
Cellular mechanisms and regulation of sodium (Na) and chloride (Cl) transport by thick ascending limb (TAL) cells. Na, Cl, and potassium (K) enter cells by way of the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) at the apical membrane. K recycles back through apical membrane K channels (ROMK) to permit continued operation of the transporter. In this nephron segment, the asymmetric operations of the luminal K channel and the basolateral chloride channel generate a transepithelial voltage, oriented with the lumen positive. This voltage drives paracellular Na absorption. Although arginine vasopressin (AVP) is known to stimulate Na reabsorption by TAL cells in some species, data from studies in human subjects suggest AVP has minimal or no effect [31,32]. The effect of AVP is mediated by way of production of cyclic adenosine monophosphate (cAMP). Prostaglandin E2 (PGE2) and cytochrome P450 (c-P450) metabolites of arachidonic acid (20-HETE [hydroxy-eicosatetraenoic acid] and 20-COOH-AA) inhibit transepithelial NaCl transport, at least in part by inhibiting the Na-K-2Cl cotransporter [33-35]. PGE2 also inhibits vasopressin-stimulated Na transport, in part by activating Gj and inhibiting adenylyl cyclase . Increases in medullary NaCl concentration may activate transepithelial Na transport by increasing production of PGE2. Inset A, Regulation of NKCC2 by chronic Na delivery. Animals were treated with 0.16 mol NaCl or water as drinking fluid for 2 weeks. The Western blot shows upregulation of NKCC2 in the group treated with saline . Gj—inhibitory G protein; PR—prostaglandin receptor; V2— AVP receptors. (Modified from Ecelbarger .)
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