title: Effects of angiotensin II on kinase-mediated sodium and potassium transport in the distal nephron.
abstract: OBJECTIVE
  The aim is to review the recently reported effects of angiotensin II (Ang II) on sodium and potassium transport in the aldosterone-sensitive distal nephron, including the signaling pathways between receptor and transporter, and the (patho)physiological implications of these findings.
  
  
  RESULTS
  Ang II can activate the sodium chloride cotransporter (NCC) through phosphorylation by Ste20-related, proline-alanine rich kinase (SPAK), an effect that is independent of aldosterone but dependent on with no lysine kinase 4 (WNK4). A low-sodium diet (high Ang II) activates NCC, whereas a high-potassium diet (low Ang II) inhibits NCC. NCC activation also contributes to Ang-II-mediated hypertension. Ang II also activates the epithelial sodium channel (ENaC) additively to aldosterone, and this effect appears to be mediated through protein kinase C and superoxide generation by nicotinamide adenine dinucleotide phosphate oxidase. While aldosterone activates the renal outer medullary potassium channel (ROMK), this channel is inhibited by Ang II. The key kinase responsible for this effect is c-Src, which phosphorylates ROMK and leaves WNK4 unphosphorylated to further inhibit ROMK.
  
  
  CONCLUSIONS
  The effects of Ang II on NCC, ENaC, and ROMK help explain the renal response to hypovolemia which is to conserve both sodium and potassium. Pathophysiologically, Ang-II-induced activation of NCC appears to contribute to salt-sensitive hypertension.
authors.affiliation: Department of Internal Medicine, Nephrology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Nils
authors.initials: N
authors.lastname: van der Lubbe
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006947:Hyperkalemia / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D020896:Hypovolemia / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000378:metabolism; D011188:Potassium / Q000493:pharmacokinetics; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000493:pharmacokinetics; D049992:Sodium Chloride Symporters / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D024661:Potassium Channels, Inwardly Rectifying; D049992:Sodium Chloride Symporters; D000804:Angiotensin II; D000450:Aldosterone; D012964:Sodium; D011188:Potassium