Title: Magnesium-deficiency-enhanced Post-ischemic Myocardial Injury is Reduced by Substance P Receptor Blockade
Abstract: <h2>Abstract</h2> Dietary Mg-deficiency increases the susceptibility of rat hearts to ischemia–reperfusion (I–R) injury<i>in vitro</i>, and also promotes substance P-associated neurogenic inflammation<i>in vivo.</i>The relationship between Mg-deficiency-induced neurogenic inflammation and the subsequently-enhanced free radical-mediated oxidative and functional injury during I–R was examined using the substance P receptor antagonist, L-703,606. Rats maintained on 3-week Mg-deficient (MgD; <1.8 mmol Mg/kg food) or Mg-sufficient (MgS; 25 mmol Mg/kg) diets were treated during this time with either L-703,606 (1.0 or 3.5 mg/sustained-release pellet, s.c.) or a placebo, prior to isolated perfused I–R. Post-ischemic functional recovery (pressure–volume work), myocardial effluent lactate dehydrogenase (LDH) activity, and lipid hydroperoxides (LOOH) were assessed after 30-min global ischemia. Lipid peroxidation-derived free radical production was monitored by<i>α</i>-phenyl-N-t-butylnitrone (PBN) spin trap infusion (2–3 mmfinal) and toluene-extracted effluents were analyzed by electron spin resonance (ESR) spectroscopy. PBN/alkoxyl adducts (<i>α</i><sub>H</sub>=1.89–1.93 G,<i>α</i><sub>N</sub>=13.58–13.63 G) were the dominant ESR signals detected in MgS and MgD I–R hearts; however, MgD hearts exhibited greater total LOOH (2.9× higher) and alkoxyl adduct production (2.3×higher), higher tissue LDH release (1.8×) and lower functional recovery (51% less) than MgS hearts. MgD rats treated with L-703,606 displayed a dose-dependent improvement in myocardial functional recovery (1.5–2×higher), and reductions in LDH release (42–59% lower), total LOOH content (36–73% lower) and alkoxyl production (40–65% lower). Interestingly, L-703,606 treatment did not reduce functional impairment or lessen the tissue and oxidative injury experienced by MgS I–R hearts. These findings suggest that L-703,606 reduced oxidative injury and improved functional recovery of MgD I–R hearts by retarding substance P-mediated inflammatory/pro-oxidant events during the<i>in vivo</i>development of Mg-deficiency.
Publication Year: 1997
Publication Date: 1997-01-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 45
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