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The nerve-heart connection in the pro-oxidant response to Mg-deficiency

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Abstract

Magnesium is a micronutrient essential for the normal functioning of the cardiovascular system, and Mg deficiency (MgD) is frequently associated in the clinical setting with chronic pathologies such as CHF, diabetes, hypertension, and other pathologies. Animal models of MgD have demonstrated a systemic pro-inflammatory/pro-oxidant state, involving multiple tissues/organs including neuronal, hematopoietic, cardiovascular, and gastrointestinal systems; during later stages of MgD, a cardiomyopathy develops which may result from a cascade of inflammatory events. In rodent models of dietary MgD, a significant rise in circulating levels of proinflammatory neuropeptides such as substance P (SP) and calcitonin gene-related peptide among others, was observed within days (1–7) of initiating the Mg-restricted diet, and implicated a neurogenic trigger for the subsequent inflammatory events; this early “neurogenic inflammation” phase may be mediated in part, by the Mg-gated N-methyl-D-aspartate (NMDA) receptor/channel complex. Deregulation of the NMDA receptor may trigger the abrupt release of neuronal SP from the sensory-motor C-fibers to promote the subsequent pro-inflammatory changes: elevations in circulating inflammatory cells, inflammatory cytokines, histamine, and PGE2 levels, as well as formation of nitric oxide, reactive oxygen species, lipid peroxidation products, and depletion of key endogenous antioxidants. Concurrent elevations of tissue CD14, a high affinity receptor for lipopolyssacharide, suggest that intestinal permeability may be compromised leading to endotoxemia. If exposure to these early (1–3 weeks MgD) inflammatory/pro-oxidant events becomes prolonged, this might lead to impaired cardiac function, and when co-existing with other pathologies, may enhance the risk of developing chronic heart failure.

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Authors and Affiliations

  1. Div. of Experimental Medicine, Dept. of Biochemistry & Molecular Biology, Washington

    Maria Isabel Tejero-Taldo, Jay Harlan Kramer, Iu Tong Mak, Andrei M. Komarov & William Bernard Weglicki

  2. Dept. of Medicine, Washington

    William Bernard Weglicki

  3. Div. of Experimental Medicine, Dept. of Biochemistry & Molecular Biology, The George Washington University Medical Center, 2300 I ST, N.W., Washington, D.C., 20037

    Maria Isabel Tejero-Taldo

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  1. Maria Isabel Tejero-Taldo
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  2. Jay Harlan Kramer
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Correspondence to Maria Isabel Tejero-Taldo.

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Tejero-Taldo, M.I., Kramer, J.H., Mak, I.T. et al. The nerve-heart connection in the pro-oxidant response to Mg-deficiency. Heart Fail Rev 11, 35–44 (2006). https://doi.org/10.1007/s10741-006-9191-7

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