Effects of dietary sodium and magnesium on cyclosporin A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats.
Arterial hypertension, nephrotoxicity, and magnesium loss are common side effects of the immunosuppressive agent cyclosporin A (CsA). In the present study, the effects of dietary sodium and magnesium on CsA toxicity were examined in spontaneously hypertensive rats. A 6-week treatment with CsA during a moderately low-sodium diet (Na 0.3%, Mg 0.2% of the dry weight of the chow) raised blood pressure only slightly, without evidence of nephrotoxicity. By contrast, CsA during a high-sodium diet (Na 2.6%) produced a pronounced rise in blood pressure as well as marked nephrotoxicity, comprising decreased creatinine clearance, increased levels of serum creatinine and urea, and increased urinary protein excretion. During the high-sodium diet, CsA decreased myocardial and bone magnesium concentration and increased myocardial and renal calcium concentration. Magnesium supplementation (Mg 0.6%) protected against the CsA-induced hypertension and nephrotoxicity during the high-sodium diet. Magnesium supplementation also completely prevented the CsA-induced myocardial magnesium depletion and calcium accumulation in the heart and kidney during the high-sodium diet. Our findings indicate a detrimental interaction between increased sodium intake and CsA treatment and a marked protection by concomitant oral magnesium supplementation.
Mervaala
E M
EM
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. eero.mervaala@helsinki.fi
Pere
A K
AK
Lindgren
L
L
Laakso
J
J
Teräväinen
T L
TL
Karjala
K
K
Vapaatalo
H
H
Ahonen
J
J
Karppanen
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006973:Hypertension / Q000139:chemically induced*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism*; D008274:Magnesium / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*
D007166:Immunosuppressive Agents; D012982:Sodium, Dietary; D016572:Cyclosporine; D008274:Magnesium