Volume 58, Issue 6, Pages 2462-2472 (December 2000) Dietary potassium and magnesium supplementation in cyclosporine-induced hypertension and nephrotoxicity  Anna-Kaisa Pere, Leena Lindgren, Päivi Tuomainen, Leena Krogerus, Pekka Rauhala, Juha Laakso, Heikki Karppanen, Heikki Vapaatalo, Juhani Ahonen, Eero M.A. Mervaala  Kidney International  Volume 58, Issue 6, Pages 2462-2472 (December 2000) DOI: 10.1046/j.1523-1755.2000.00429.x Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 1 Line plots show development of hypertension in cyclosporine A (CsA)-treated spontaneously hypertensive rats (SHRs) during different diets for six weeks. Symbols are: (•) high-sodium diet; (○) high-sodium/high-potassium diet; (□) high-sodium/high-magnesium diet; (▪) high-sodium/high-potassium/high-magnesium diet. Potassium and magnesium supplementation, alone and in combination, decreased blood pressure in CsA-treated SHR on high-sodium diet. *P < 0.05 compared with all other groups. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 2 Left ventricle hypertrophy (LVH), expressed as left ventricle wet weight (A) and left ventricle wet weight-to-body weight ratio (B) in CsA-treated SHR during different diets for six weeks. Magnesium supplementation, alone and in combination with potassium, ameliorated LVH in CsA-treated SHRs on high-sodium diet. *P < 0.05 compared with the high-sodium group; $P < 0.05 compared with the high-sodium/high-magnesium group; §P < 0.05 compared with the high-sodium/high-potassium group. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 3 Line plots show heart rates (HRs) in CsA-treated SHRs during different diets for six weeks. Abbreviations are given in Figure 1. CsA increased HR regardless of the diet. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 4 Representative photomicrographs from the kidneys of CsA-treated SHR on high-sodium diet (A) and normotensive WKY rat (B). CsA-treated SHR on high-sodium diet showed severe thickening of the media of afferent arteriole and fibrinoid necrosis of the arteriolar wall. Potassium only partially prevented CsA-induced renal damage. Magnesium supplementation, alone and in combination, prevented the CsA-induced morphological changes in the kidney (C). *P < 0.05 compared with the high-sodium group; §P < 0.05 compared with the high-sodium/high-potassium group. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 5 Line plots show the development of proteinuria (A) and urinary NAG excretion (B) in CsA-treated SHRs during different diets for six weeks. Symbols are: (•) high-sodium diet; (○) high-sodium/high-potassium diet; (□) high-sodium/high-magnesium diet; (▪) high-sodium/high-potassium/high-magnesium diet. Potassium partially prevented the development of proteinuria, whereas magnesium supplementation, alone and in combination, was more effective. CsA increased urinary NAG excretion irrespective of the diet. *P < 0.05 vs. all other groups, §P < 0.05 vs. high-magnesium and high-magnesium/high-potassium diet groups. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 6 Twenty-four–hour urinary dopamine excretion in CsA-treated SHR during different diets for six weeks. Magnesium supplementation, alone and in combination with potassium, prevented the suppression of urinary dopamine excretion in CsA-treated SHRs on high-sodium diet. *P < 0.05 compared with the high-sodium diet group; §P < 0.05 compared with the high-sodium/high-potassium diet group. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 7 Serum-free magnesium concentration (iMg; A) and bone magnesium concentration (B), in CsA-treated SHR during different diets for six weeks. Magnesium supplementation, alone and in combination with potassium, increased iMg and bone magnesium concentrations in CsA-treated SHR on high-sodium diet. *P < 0.05 compared with high-sodium/high-potassium diet groups. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions

Figure 8 Serum cholesterol concentration in CsA-treated SHRs during different diets for six weeks. Serum cholesterol concentration in CsA-treated SHR on high-sodium diet, both in the presence and in the absence of potassium supplementation, was higher compared with magnesium-supplemented and magnesium + potassium-supplemented SHRs. *P < 0.05 compared with the high-sodium diet group; §P < 0.05 compared with the high-sodium/high-potassium diet group. Means ± SEM are given, N = 8 to 10 in each group. Kidney International 2000 58, 2462-2472DOI: (10.1046/j.1523-1755.2000.00429.x) Copyright © 2000 International Society of Nephrology Terms and Conditions