title: Abnormal increase in urinary aquaporin-2 excretion in response to hypertonic saline in essential hypertension.
abstract: BACKGROUND
  Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.
  
  
  METHODS
  We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2(CR), u-ENaC(β-CR)), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FE(Na)), free water clearance (C(H2O)), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide (ANP, BNP) in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).
  
  
  RESULTS
  At baseline, no differences in u-AQP2(CR) or u-ENaC(β-CR) were measured between patients and controls. U-AQP2(CR) increased significantly more after saline in patients than controls, whereas u-ENaC(β-CR) increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2(CR) response.
  
  
  CONCLUSIONS
  No differences were found in u-AQP2(CR) and u-ENaC(β-CR) between patients and controls at baseline. However, in response to saline, u-AQP2(CR) was abnormally increased in patients, whereas the u-ENaC(β-CR) response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent. Clinicaltrial.gov identifier: NCT00345124.
authors.affiliation: Department of Medical Research, Holstebro Hospital, Holstebro, Denmark. ccannillo@hotmail.com
authors.forename: Carolina Cannillo
authors.initials: CC
authors.lastname: Graffe
authors.forename: Jesper Nørgaard
authors.initials: JN
authors.lastname: Bech
authors.forename: Thomas Guldager
authors.initials: TG
authors.lastname: Lauridsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Vase
authors.forename: Erling Bjerregaard
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D051399:Aquaporin 2 / Q000652:urine*; D009320:Atrial Natriuretic Factor / Q000097:blood; D018592:Cross-Over Studies; D000242:Cyclic AMP / Q000652:urine; D015232:Dinoprostone / Q000652:urine; D053503:Epithelial Sodium Channels / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology / Q000652:urine*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009994:Osmolar Concentration; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary; D014667:Vasopressins / Q000097:blood
chemical_list: D051399:Aquaporin 2; D053503:Epithelial Sodium Channels; D012982:Sodium, Dietary; D014667:Vasopressins; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012964:Sodium; D000242:Cyclic AMP; D012083:Renin; D015232:Dinoprostone