title: Effects of dietary sodium and magnesium on cyclosporin A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats.
abstract: 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.
authors.affiliation: Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. eero.mervaala@helsinki.fi
authors.forename: E M
authors.initials: EM
authors.lastname: Mervaala
authors.forename: A K
authors.initials: AK
authors.lastname: Pere
authors.forename: L
authors.initials: L
authors.lastname: Lindgren
authors.forename: J
authors.initials: J
authors.lastname: Laakso
authors.forename: T L
authors.initials: TL
authors.lastname: Teräväinen
authors.forename: K
authors.initials: K
authors.lastname: Karjala
authors.forename: H
authors.initials: H
authors.lastname: Vapaatalo
authors.forename: J
authors.initials: J
authors.lastname: Ahonen
authors.forename: H
authors.initials: H
authors.lastname: Karppanen
mesh_terms: 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*
chemical_list: D007166:Immunosuppressive Agents; D012982:Sodium, Dietary; D016572:Cyclosporine; D008274:Magnesium