Magnesium supplementation prevents angiotensin II-induced myocardial damage and CTGF overexpression
Authors
- P. Finckenberg
- S. Merasto
- M. Louhelainen
- L. Lindgren
- H. Vapaatalo
- D.N. Mueller
- F.C. Luft
- E.M. Mervaala
Journal
- Journal of Hypertension
Citation
- J Hypertens 23: 375-380
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.