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J Mol Cell Cardiol. 1997 Jan;29(1):97-110.

Magnesium-deficiency-enhanced post-ischemic myocardial injury is reduced by substance P receptor blockade.

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  • 1Division of Experimental Medicine, The George Washington University Medical Center, Washington, DC 20037, USA.

Abstract

Dietary Mg-deficiency increases the susceptibility of rat hearts to ischemia-reperfusion (I-R) injury in vitro, and also promotes substance P-associated neurogenic inflammation in vivo. 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 alpha-phenyl-N-t-butylnitrone (PBN) spin trap infusion (2-3 mM final) and toluene-extracted effluents were analyzed by electron spin resonance (ESR) spectroscopy. PBN/alkoxyl adducts (alpha(H) = 1.89-1.93 G, alpha(N) = 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 x higher) and alkoxyl adduct production (2.3 x higher), higher tissue LDH release (1.8 x ) 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 x 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 in vivo development of Mg-deficiency.

PMID:
9040025
DOI:
10.1006/jmcc.1996.0255
[PubMed - indexed for MEDLINE]
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