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Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression

Item Type:Article
Title:Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression
Creators Name:Finckenberg, P. and Merasto, S. and Louhelainen, M. and Lindgren, L. and Vapaatalo, H. and Mueller, D.N. and Luft, F.C. and Mervaala, E.M.
Abstract:OBJECTIVES AND DESIGN: Magnesium deficiency promotes vasoconstriction and myocardial damage. Recent studies provide evidence that Ang II mobilizes intracellular Mg through AT1 receptor-mediated pathways. We tested the hypothesis of whether magnesium supplementation prevents Ang II-induced myocardial damage and induction of the profibrotic connective tissue growth factor (CTGF). METHODS: Four-week-old double transgenic rats harboring human renin and angiotensinogen genes (dTGR) were given dietary magnesium supplementation (0.6%) for 3 weeks. Control dTGR and normotensive Sprague-Dawley (SD) rats received normal diet (Mg 0.2%). Histopathological, immunohistochemical and mRNA analysis were used to detect the treatment-related effects of dietary magnesium in dTGR. RESULTS: Magnesium (Mg) supplementation decreased blood pressure, ameliorated cardiac hypertrophy, protected against the development of Ang II-induced myocardial damage and increased serum ionized Mg2+ concentration (all variables P < 0.05). There was no difference in serum ionized Mg2+ concentration between dTGR and SD rats. Myocardial connective tissue growth factor (CTGF) mRNA and protein expressions were increased by 300% in dTGR (P < 0.05), especially in areas with myocardial infarctions and vascular inflammation. Magnesium supplementation prevented Ang II-induced myocardial CTGF overexpression (P < 0.05). Magnesium supplementation also improved the therapeutic effects of the calcineurin inhibitor tacrolimus, which produced marked hypomagnesemia when given as monotherapy. CONCLUSION: Our findings suggest a salutary effect for magnesium supplementation in the treatment of Ang II-induced myocardial complications.
Keywords:Angiotensin II, Connective tissue growth factor, Magnesium, Myocardial fibrosis, Tacrolimus, Animals, Rats
Source:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins
Page Range:375-380
Date:1 January 2005
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