The nerve-heart connection in the pro-oxidant response to Mg-deficiency.
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 PGE(2) 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.
Tejero-Taldo
Maria Isabel
MI
Dept. of Biochemistry & Molecular Biology, Div. of Experimental Medicine, The George Washington University Medical Center, Washington, DC 20037, USA. phymit@gwumc.edu
Kramer
Jay Harlan
JH
Mak
Iu Tong
IuT
Komarov
Andrei M
AM
Weglicki
William Bernard
WB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008275:Magnesium Deficiency / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013373:Substance P / Q000502:physiology
D000975:Antioxidants; D064729:Neurokinin-1 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D013373:Substance P