title: Adrenal aldosterone biosynthesis is elevated in a model of chronic renal failure--role of local adrenal renin-angiotensin system.
abstract: BACKGROUND
  Aldosterone seems to play a role in the development of chronic renal failure and proteinuria. We investigated the adrenal aldosterone production and the adrenal renin-angiotensin system (RAS) in rats with 5/6 nephrectomy with and without spironolactone treatment.
  
  
  METHODS
  Sprague-Dawley rats underwent 5/6, 4/6 nephrectomy, heminephrectomy and sham operation. After 1 and 4 weeks creatinine clearance, urinary protein excretion, plasma aldosterone concentration, and plasma renin activity were measured. In adrenals mRNA expression of aldosterone synthase (CYP11B2) and genes of the RAS were measured.
  
  
  RESULTS
  Creatinine clearance was significantly decreased and proteinuria significantly elevated in 5/6 nephrectomy. Treatment with spironolactone significantly reduced proteinuria after 8 but not after 30 days. With reduction of renal mass, renal renin mRNA and plasma renin activity were reduced significantly. In early 5/6 nephrectomy plasma aldosterone concentration was increased and in parallel adrenal CYP11B2 mRNA was increased significantly. Both were further augmented by spironolactone. Adrenal renin was up-regulated in 5/6 nephrectomy and further stimulated with spironolactone, possibly serving as a stimulus for the adrenal aldosterone synthesis.
  
  
  CONCLUSIONS
  In early chronic renal failure after 5/6 nephrectomy adrenal aldosterone production is elevated despite a marked decrease of plasma renin activity. An up-regulated adrenal RAS may contribute to the observed increase in aldosterone.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany.
authors.forename: Dierk H
authors.initials: DH
authors.lastname: Endemann
authors.forename: Konrad
authors.initials: K
authors.lastname: Wolf
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Boeger
authors.forename: Günter A J
authors.initials: GA
authors.lastname: Riegger
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000503:physiopathology*; D000450:Aldosterone / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology* / Q000652:urine; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000450:Aldosterone; D012083:Renin