Media calcification, low erythrocyte magnesium, altered plasma magnesium, and calcium homeostasis following grafting of the thoracic aorta to the infrarenal aorta in the rat--differential preventive effects of long-term oral magnesium supplementation alone and in combination with alkali.
Calcifications in arterial media are clinically well documented, but the role played by magnesium in pathophysiology and therapy is uncertain. To clarify this, an animal model in which the juxtacardial aorta was grafted to the infrarenal aorta, and the subsequent calcifications in the media of the graft and their response to oral supplementation with three magnesium-containing and alkalinizing preparations was investigated. Groups of highly inbred rats were formed as follows: sham-operation (Sham, n = 12), aorta transplantation (ATx, n = 12), ATx + magnesium citrate (MgC, n = 12), ATx + MgC + potassium citrate (MgCPC, n = 12), ATx + MgC + MgCPC (MgCPCSB, n = 12). At 84 (+/-2) days after ATx with or without treatment the following observations were made: (1) weight gain and general status were normal; (2) ATx rats developed massive media calcification, mineral accumulation in the graft, decreased erythrocyte magnesium and plasma parathyroid hormone, and increased plasma ionized magnesium and calcium, and uric acid; (3) Mg-treated rats developed variable degrees of metabolic alkalosis, but only MgCPCSB supplementation prevented calcifications. Additional findings after ATx alone were: imbalance in endothelin and nitric oxide production, the mineral deposited in media was poorly crystallized calcium phosphate, calcium exchange between plasma and graft, and bone resorption were unchanged. The superior anti-calcification effect of MgCPCSB was characterized by complete restoration of normal extracellular mineral homeostasis and uric acid, but sub-optimal normalization of erythrocyte magnesium. It was concluded that in the rat: (1) ATx causes loss of cellular magnesium, excess of extracellular magnesium and calcium in the presence of apparently unchanged bone resorption, and increased uricemia; (2) ATx facilitates enhanced influx of calcium into vascular tissue, leading to calcium phosphate deposition in the media; (3) ATx-induced calcification is prevented by dietary supplementation with a combination of magnesium, alkali citrate and bases. Although the described circulatory model of media calcification in the rat requires further investigation, the data allow ascribing a fundamental role to magnesium and acid-base metabolism.
Schwille
P O
PO
Mineral Metabolism and Endocrine Research Laboratory, University of Erlangen, Erlangen, Germany. schwille@web.de
Schmiedl
A
A
Schwille
R
R
Brunner
P
P
Kissler
H
H
Cesnjevar
R
R
Gepp
H
H
D000818:Animals; D001011:Aorta / Q000601:surgery; D001013:Aorta, Thoracic / Q000473:pathology* / Q000637:transplantation; D001018:Aortic Diseases / Q000097:blood / Q000473:pathology / Q000517:prevention & control; D002114:Calcinosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002118:Calcium / Q000097:blood*; D019343:Citric Acid / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism*; D006706:Homeostasis; D007668:Kidney / Q000098:blood supply; D008274:Magnesium / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008672:Metals, Alkali / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000627:therapeutic use; D019357:Potassium Citrate / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D017693:Sodium Bicarbonate / Q000627:therapeutic use; D013997:Time Factors; D017540:Tunica Media / Q000473:pathology*
D008672:Metals, Alkali; D009942:Organometallic Compounds; D019343:Citric Acid; D017693:Sodium Bicarbonate; D019357:Potassium Citrate; D008274:Magnesium; C110422:magnesium citrate; D002118:Calcium