Figure 217

Mechanisms and regulation of sodium (Na) and chloride (Cl) transport by the distal nephron. As in other nephron segments, intracellular Na concentration is maintained low by the action of the Na-K ATPase (sodium-potassium adenosine triphosphatase) pump at the basolateral cell membrane. Na enters distal convoluted tubule (DCT) cells across the luminal membrane coupled directly to chloride by way of the thiazide-sensitive Na-Cl cotransporter. Activity of the Na-Cl cotransporter appears to be stimulated by both aldosterone and angiotensin II (AII) [38-40]. Transepithelial Na transport in this segment is also stimulated by sympathetic nerves acting by way of a receptors [41,42]. The DCT is impermeable to water.

FIGURE 2-18

FIGURE 2-19

FIGURE 2-18

Principal cortical collecting tubule (CCT) cells. In these cells, sodium (Na) enters across the luminal membrane through Na channels (ENaC). The movement of cationic Na from lumen to cell depolarizes the luminal membrane, generating a transepithelial electrical gradient oriented with the lumen negative with respect to intersti-tium. This electrical gradient permits cationic potassium (K) to diffuse preferentially from cell to lumen through K channels (ROMK). Na transport is stimulated when aldosterone interacts with its intracellular receptor [43]. This effect involves both increases in the number of Na channels at the luminal membrane and increases in the number of Na-K ATPase (Sodium-potassium adenosine triphosphatase) pumps at the basolateral cell membrane. Arginine vasopressin (AVP) stimulates both Na absorption (by interacting with V2 receptors and, perhaps, Vj receptors) and water transport (by interacting with V2 receptors) [44-46]. V2 receptor stimulation leads to insertion of water channels (aquapor-in 2) into the luminal membrane [47]. V2 receptor stimulation is modified by PGE2 and <X2 agonists that interact with a receptor that stimulates G( [48]. AC—adenylyl cyclase; ATP—adenosine triphosphate; cAMP—cyclic adenosine monophosphate; CCT—cor-tical collecting tubule; Gi—inhibitory G protein; Gs—stimulatory G protein; R—Ri receptor.

FIGURE 2-19

Cellular mechanism of the medullary collecting tubule (MCT). Sodium (Na) and water are reabsorbed along the MCT. Atrial natriuretic peptide (ANP) is the best-characterized hormone that affects Na absorption along this segment [22]. Data on the effects of argi-nine vasopressin (AVP) and aldosterone are not as consistent [46,49]. Prostaglandin E2 (PGE2) inhibits Na transport by inner medullary collecting duct cells and may be an important intracellu-lar mediator for the actions of endothelin and interleukin-1 [50,51]. ANP inhibits medullary Na transport by interacting with a G-pro-tein-coupled receptor that generates cyclic guanosine monophosphate (cGMP). This second messenger inhibits a luminal Na channel that is distinct from the Na channel expressed by the principal cells of the cortical collecting tubule, as shown in Figure 2-18 [52,53]. Under normal circumstances, ANP also increases the glomerular filtration rate (GFR) and inhibits Na transport by way of the effects on the renin-angiotensin-aldosterone axis, as shown in Figures 2-7 to 2-10. These effects increase Na delivery to the MCT. The combination of increased distal Na delivery and inhibited distal reabsorption leads to natriuresis. In patients with congestive heart failure, distal Na delivery remains depressed despite high levels of circulating ANP. Thus, inhibition of apical Na entry does not lead to natri-uresis, despite high levels of MCT cGMP. AR—ANP receptor; GC—guanylyl cyclase; K—potassium; V2—receptors.

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