High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure.
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.
Pörsti
Ilkka
I
Department of Internal Medicine, University of Tampere, Tampere, Finland. ilkka.porsti@uta.fi
Fan
Meng
M
Kööbi
Peeter
P
Jolma
Pasi
P
Kalliovalkama
Jarkko
J
Vehmas
Tuija I
TI
Helin
Heikki
H
Holthöfer
Harry
H
Mervaala
Eero
E
Nyman
Tuulikki
T
Tikkanen
Ilkka
I
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
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