title: Mechanisms of sodium-chloride cotransporter modulation by angiotensin II.
abstract: OBJECTIVE
  The renin-angiotensin-aldosterone system is an important modulator of renal salt excretion and arterial pressure. An important body of evidence now supports that angiotensin II (AngII) modulates the function of the renal sodium-chloride cotransporter (NCC), independently of aldosterone. Here we summarize these data, as well as recent knowledge regarding the intracellular mechanisms underlying this effect.
  
  
  RESULTS
  AngII has the ability to modulate NCC total expression, apical localization, and phosphorylation by aldosterone-independent mechanisms. Recent evidence suggests that these effects are achieved through modulation of the With No Lysine kinase 4 (WNK4) and Ste20-related, proline-alanine-rich kinase (SPAK) pathway. Missense mutations in the acidic domain of WNK4, which are the cause of one of the subtypes of pseudohypoaldosteronism type II (PHAII), could be mimicking the effect produced by AngII on NCC through the WNK4-SPAK pathway. WNK4 activity has been shown to vary in response to changes in calcium concentration and PHAII-WNK4 mutants apparently lose this ability. Thus, AngII may regulate WNK4 activity through the modulation of intracellular calcium concentration.
  
  
  CONCLUSIONS
  Modulation of WNK4 activity by AngII underlies the effects of AngII on NCC activity and this is probably important for the stimulation of renal sodium retention, as well as for the prevention of potassium loss, during hypovolemia.
authors: Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico City, Mexico.
authors: María
authors: M
authors: Castañeda-Bueno
authors: Gerardo
authors: G
authors: Gamba
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D006801:Humans; D011546:Pseudohypoaldosteronism / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D049992:Sodium Chloride Symporters / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism
chemical_list: D049992:Sodium Chloride Symporters; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D000450:Aldosterone