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High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsIlkka Pörsti, Meng Fan, Peeter Kööbi, Pasi Jolma, Jarkko Kalliovalkama, Tuija I Vehmas, Heikki Helin, Harry Holthöfer, Eero Mervaala, Tuulikki Nyman, Ilkka Tikkanen
JournalKidney international (Kidney Int) Vol. 66 Issue 6 Pg. 2155-66 (Dec 2004) ISSN: 0085-2538 [Print] United States
PMID15569305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CCN2 protein, rat
  • Calcium, Dietary
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Parathyroid Hormone
  • Phosphates
  • Connective Tissue Growth Factor
  • Peptidyl-Dipeptidase A
Topics
  • Albuminuria (drug therapy, metabolism, pathology)
  • Animals
  • Aorta (pathology)
  • Calcium, Dietary (pharmacology)
  • Connective Tissue Growth Factor
  • Down-Regulation (drug effects)
  • Immediate-Early Proteins (metabolism)
  • Intercellular Signaling Peptides and Proteins (metabolism)
  • Kidney (enzymology, pathology)
  • Male
  • Parathyroid Hormone (blood)
  • Peptidyl-Dipeptidase A (metabolism)
  • Phosphates (blood)
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency (drug therapy, metabolism, pathology)
  • Renin-Angiotensin System (drug effects, physiology)

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