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

• Published in: Kidney international Vol. 66; no. 6; pp. 2155 - 2166
• Main Authors: Pörsti, Ilkka, Fan, Meng, Kööbi, Peeter, Jolma, Pasi, Kalliovalkama, Jarkko, Vehmas, Tuija I., Helin, Heikki, Holthöfer, Harry, Mervaala, Eero, Nyman, Tuulikki, Tikkanen, Ilkka
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2004; Nature Publishing; Elsevier Limited
• Subjects: Albuminuria - drug therapy; Albuminuria - metabolism; Albuminuria - pathology; angiotensin-converting enzyme; Animals; Aorta - pathology; Biological and medical sciences; calcium diet; Calcium, Dietary - pharmacology; Connective Tissue Growth Factor; Down-Regulation - drug effects; Immediate-Early Proteins - metabolism; Intercellular Signaling Peptides and Proteins - metabolism; Kidney - enzymology; Kidney - pathology; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; parathyroid hormone; Parathyroid Hormone - blood; Peptidyl-Dipeptidase A - metabolism; phosphate; Phosphates - blood; Rats; Rats, Sprague-Dawley; Renal failure; Renal Insufficiency - drug therapy; Renal Insufficiency - metabolism; Renal Insufficiency - pathology; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; phosphate; renal failure; parathyroid hormone; calcium diet; angiotensin-converting enzyme; Kidney disease; High; Phosphates; Nephrology; Urinary system disease; Calcium; Enzyme; Experimental study; Inorganic element; Urology; Feeding; Peptidases; Parathormone; Regulation(control); Urinary system; Diet; Parathyroid hormone; Peptidyl-dipeptidase A; Renal failure; Hydrolases; Peptidyl-dipeptidases
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1111/j.1523-1755.2004.66006.x

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