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(Hypertension. 1997;29:822-827.)
© 1997 American Heart Association, Inc.

Articles

Effects of Dietary Sodium and Magnesium on Cyclosporin A–Induced Hypertension and Nephrotoxicity in Spontaneously Hypertensive Rats

Eero M.A. Mervaala; Anna-Kaisa Pere; Leena Lindgren; Juha Laakso; Terttu-Liisa Teravainen; Kirsi Karjala; Heikki Vapaatalo; Juhani Ahonen; Heikki Karppanen

the Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki (E.M.A.M., J.L., T.-L.T., K.K., H.V., H.K.); the Division of Transplantation Surgery, Fourth Department of Surgery, Helsinki University Central Hospital (A.-K.P., L.L., J.A.); Mila Ltd (J.L.); and the Department of Physiology, Faculty of Veterinary Medicine, University of Helsinki (T.-L.T.), Finland.

Correspondence to Eero Mervaala, MD, PhD, Institute of Biomedicine, Department of Pharmacology and Toxicology, PO Box 8, FIN-00014 University of Helsinki, Finland. E-mail eero.mervaala@helsinki.fi

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.

Key Words: cyclosporine • rats, spontaneously hypertensive • hypertrophy, left ventricular • proteinuria • sodium • magnesium • calcium

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