Abstract
Hypomagnesemia occurs clinically as a result of restricted dietary intake, Mg-wasting drug therapies, chronic disease status and may be a risk factor in patients with cardiovascular disorders. Dietary restriction of magnesium (Mg deficiency) in animal models produced a pro-inflammatory/pro-oxidant condition, involving hematopoietic, neuronal, cardiovascular, renal and other systems. In Mg-deficient rodents, early elevations in circulating levels of the neuropeptide, substance P (SP) may trigger subsequent deleterious inflammatory/oxidative/nitrosative stress events. Evidence also suggests that activity of neutral endopeptidase (NEP, neprilysin), the major SP-degrading enzyme, may be impaired during later stages of Mg deficiency, and this may sustain the neurogenic inflammatory response. In this article, experimental findings using substance P receptor blockade, NEP inhibition, and N-methyl-D-aspartate (NMDA) receptor blockade demonstrated the connection between hypomagnesemia, neurogenic inflammation, oxidative stress and enhanced cardiac dysfunction. Proof of concept concerning neurogenic inflammation is provided using an isolated perfused rat heart model exposed to acute reductions in perfusate magnesium concentrations.
Highlights
Hypomagnesemia is frequently associated with clinical disorders such as diabetes, metabolic syndrome, alcoholism, HIV-1 infection, cancer, and cardiovascular diseases, or as a consequence of low dietary magnesium (Mg) intake, GI/renal malabsorption, or Mg-wasting drug therapies [1,2,3].Since hypomagnesemia can occur in patients with restricted dietary magnesium intake and magnesium-wasting drugs, clinically significant hypomagnesemia can be a problem, especially in patients with heart disease
This preceded the elevations in circulating inflammatory cytokines (IL-1, IL-6, and TNF α) which began after dietary day 12
A second rise in circulating substance P (SP) began after two weeks of Mg deficiency, coinciding with inactivation of neutral endopeptidase (NEP), the primary SP-degrading protease [21,22]
Summary
Hypomagnesemia is frequently associated with clinical disorders such as diabetes, metabolic syndrome, alcoholism, HIV-1 infection, cancer, and cardiovascular diseases, or as a consequence of low dietary magnesium (Mg) intake, GI/renal malabsorption, or Mg-wasting drug therapies [1,2,3]. Since hypomagnesemia can occur in patients with restricted dietary magnesium intake and magnesium-wasting drugs, clinically significant hypomagnesemia can be a problem, especially in patients with heart disease. In one report [4], 10~20% of hospitalized patients had hypomagnesemia, and this was most common in critically ill patients, and in those with heart failure. Hypomagnesemia has been linked to cardiac arrhythmias and vasospasm and may be a risk factor for patients with cardiovascular disease [3,5,6].
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