Detrimental effect of dietary sodium and beneficial effect of dietary magnesium on glomerular changes in cyclosporin-A-treated spontaneously hypertensive rats.

Abstract

Cyclosporin A (CsA) causes renal magnesium wasting, hypertension, and occasionally irreversible renal damage. We examined the effect of dietary sodium and magnesium on renal histology in spontaneously hypertensive rats (SHR) receiving CsA. Forty-six 8-week-old SHR were divided into six groups and given different dietary levels of sodium (low 0.3%, high 2.6%) and magnesium (low 0.2%, high 0.6%). Low-dose CsA (5 mg/kg/d) was given subcutaneously for 6 weeks in four groups. Systolic blood pressure, serum creatinine, degree of proteinuria, and renal tissue CsA and calcium concentrations were determined. Kidney wet weight to total body-weight ratio was calculated as an index of renal hypertrophy. Renal histological alterations were scored according to glomerular changes: 100 glomeruli were assigned for severity of change a score from 0 to 3. The number of affected glomeruli was multiplied by the damage score to obtain a damage index. In the CsA-treated high-sodium diet group systolic blood pressure and glomerular damage index were increased, and renal hypertrophy was the most common. These changes were prevented by oral magnesium supplementation. The glomerular damage index correlated positively with increases in systolic blood pressure, serum creatinine, proteinuria, and renal calcium concentration. Dietary sodium enhanced CsA-induced functional and morphological renal changes in SHR and aggravated hypertensive renal arteriolar and glomerular lesions. Dietary magnesium supplementation protected against the deleterious effects of sodium and CsA.