Dietary Magnesium Intake Influences Circulating Pro-Inflammatory Neuropeptide Levels and Loss of Myocardial Tolerance to Postischemic Stress

Abstract

Severe dietary Mg restriction (Mg₉, 9% of recommended daily allowance [RDA], plasma Mg = 0.25 mM) induces a proinflammatory neurogenic response in rats (substance P [SP]), and the associated increases in oxidative stress in vivo and cardiac susceptibility to ischemla/reperfusion (I/R) injury were previously shown to be attenuated by SP receptor blockade and antioxidant treatment. The present study assessed if less severe dietary Mg restriction modulates the extent of both the neurogenic/oxidative responses in vivo and I/R injury in vitro. Male Sprague-Dawley rats maintained on Mg₄₀ (40% RDA, plasma Mg = 0.6 mM) or Mg₁₀₀ (100% RDA, plasma Mg = 0.8 mM) diets were assessed for plasma SP levels (CHEM-ELISA) during the first 3 weeks and were compared with the Mg₉ group; red blood cell (RBC) glutathione and plasma malondialdehyde levels were compared at 3 weeks in Mg₉, Mg₂₀ (plasma Mg = 0.4 mM), Mg₄₀, and Mg₁₀₀ rats; and 40-min global ischemia/30-min reperfuslon hearts from 7-week-old Mg₂₀, Mg₄₀, and Mg₁₀₀ rats were compared with respect to functional recovery (cardiac work, and diastolic, systolic, and developed pressures), tissue LDH release, and free radical production (ESR spectroscopy and α-phenyl-N-tert butyinitrone [PBN; 3 mM] spin trapping). The Mg₄₀ diet induced smaller elevations in plasma SP (50% lower) compared with Mg₉, but with a nearly identical time course. RBC glutathione and plasma malondialdehyde levels revealed a direct relationship between the severity of oxidative stress and hypomagnesemia. The dominant lipid free radical species detected in all I/R groups was the alkoxyl radical (PBN/alkoxyl: α_H = 1.93 G, α_N = 13.63 G); however, Mg₄₀ and Mg₂₀ hearts exhibited 2.7- and 3.9-fold higher alkoxyl levels, 40% and 65% greater LDH release, and lower functional recovery (Mg₂₀ < Mg₄₀) compared with Mg₁₀₀. Our data suggest that varying dietary Mg intake directly influences the magnitude of the neurogenic/oxidative responses in vivo and the resultant myocardial tolerance to I/R Stress.