title: High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure.
abstract: BACKGROUND
  Calcium salts are used as phosphate binders in renal failure, while high calcium diet also improves vasorelaxation and enhances natriuresis. The influences of calcium intake on renal renin-angiotensin system (RAS) are largely unknown.
  
  
  METHODS
  Four weeks after NTX, rats were put on 3.0% or 0.3% calcium diet for 8 weeks (12-week study). In additional experiments, 15 weeks after NTX, rats were put on similar diets for 12 weeks (27-week study). Appropriate blood, urine, and kidney samples were taken. Renal angiotensin-converting enzyme (ACE) and angiotensin II receptors (AT1, AT2) were examined using autoradiography, ACE also using Western blotting, and connective tissue growth factor (CTGF) using immunohistochemistry.
  
  
  RESULTS
  In the 12-week study, albuminuria increased 5-fold in NTX rats, but only 2-fold in calcium NTX rats on 3.0% calcium. In the 27-week study, high calcium intake decreased blood pressure, retarded progression of renal failure, reduced glomerulosclerosis, interstitial damage, and aortic calcifications, and improved survival from 50% to 92% in NTX rats. In both experiments plasma parathyroid hormone and phosphate were elevated after NTX, and suppressed by high calcium diet, while kidney ACE was down-regulated by 40% or more after increased calcium intake. In the 27-week study renal CTGF was decreased and cortical AT1 receptor density reduced after high calcium diet.
  
  
  CONCLUSIONS
  High calcium diet down-regulated kidney ACE, reduced albuminuria and blood pressure, and favorably influenced kidney morphology in experimental renal failure. These findings suggest a link between calcium metabolism and kidney ACE expression, which may play a role in the progression of renal damage.
authors.affiliation: Department of Internal Medicine, University of Tampere, Tampere, Finland. ilkka.porsti@uta.fi
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
authors.forename: Meng
authors.initials: M
authors.lastname: Fan
authors.forename: Peeter
authors.initials: P
authors.lastname: Kööbi
authors.forename: Pasi
authors.initials: P
authors.lastname: Jolma
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kalliovalkama
authors.forename: Tuija I
authors.initials: TI
authors.lastname: Vehmas
authors.forename: Heikki
authors.initials: H
authors.lastname: Helin
authors.forename: Harry
authors.initials: H
authors.lastname: Holthöfer
authors.forename: Eero
authors.initials: E
authors.lastname: Mervaala
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Nyman
authors.forename: Ilkka
authors.initials: I
authors.lastname: Tikkanen
mesh_terms: D000419:Albuminuria / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000473:pathology; D002136:Calcium, Dietary / Q000494:pharmacology*; D055513:Connective Tissue Growth Factor; D015536:Down-Regulation / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010710:Phosphates / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: C526316:CCN2 protein, rat; D002136:Calcium, Dietary; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D055513:Connective Tissue Growth Factor; D007703:Peptidyl-Dipeptidase A