Experimental Hypomagnesemia Induces Neurogenic Inflammation and Cardiac Dysfunction
Department of Biochemistry & Molecular Medicine, The George Washington University, Washington, DC 20037, USA
Division of Cardiology, Children’s National Medical Center, Washington, DC 20010, USA
Affiliate Professor of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23284, USA
Authors to whom correspondence should be addressed.
Hearts 2020, 1(2), 99-116; https://0-doi-org.brum.beds.ac.uk/10.3390/hearts1020011
Received: 23 July 2020 / Revised: 2 September 2020 / Accepted: 2 September 2020 / Published: 5 September 2020
(This article belongs to the Special Issue Nutrient Deficiency and Drug Induced Cardiac Injury and Dysfunction)
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.