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

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1997-03, Vol.29 (3), p.822-827
• Main Authors: Mervaala, Eero, Pere, Anna-Kaisa, Lindgren, Leena, Laakso, Juha, Teravainen, Terttu-Liisa, Karjala, Kirsi, Vapaatalo, Heikki, Ahonen, Juhani, Karppanen, Heikki
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Cyclosporine - toxicity; Dose-Response Relationship, Drug; Drug Interactions; Drug toxicity and drugs side effects treatment; Hypertension - chemically induced; Immunosuppressive Agents - toxicity; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Magnesium - administration & dosage; Magnesium - metabolism; Magnesium - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Sodium, Dietary - administration & dosage; Sodium, Dietary - metabolism; Sodium, Dietary - toxicity; Toxicity: urogenital system
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.29.3.822

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. (Hypertension. 1997;29:822-827.)