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Magnesium Research

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Suppression of neutrophil and endothelial activation by substance P receptor blockade in the Mg‐deficient rat Volume 16, numéro 2, June 2003

Auteurs
The George Washington University Medical Center, Department of Physiology and Experimental Medicine, Washington, DC 20037, USA

The regulatory role of substance‐P (SP) on neutrophil and endothelium activation as well as nitric oxide (NO) production induced by Mg‐deficiency was examined. Male Sprague‐Dawley rats (180 g) were fed either a Mg‐deficient (MgD) or Mg‐sufficient (MgS) diet for 3 weeks. Enriched neutrophil fractions (> 85%) isolated from whole blood of the Mg‐deficient rats displayed an 11‐fold (p < 0.001) higher basal superoxide anion producing activity (assayed as SOD‐inhibitable cytochrome c reduction) compared to that obtained from the MgS rats. Treatment of the MgD rats with the specific SP‐receptor (SPR) blocker, L‐703,606 (1 mg\kg\day as s.c. implanted sustained‐release pellets) attenuated the superoxide anion producing activity by 75% (p < 0.025). In parallel, circulating prostacyclin (PGI 2) level (assayed as 6‐keto‐PGF‐1α) was elevated 13‐fold in the MgD rats, but was reduced 90% by L‐703,606 treatment. Concomitantly, plasma NO products (nitrate + nitrite), which increased 2.2‐fold during Mg‐deficiency, were completely suppressed by the SPR blockade. When the isolated hearts were subjected to ischemia\reperfusion stress, NO products were elevated 2.4‐fold in the effluent of the MgD group compared to MgS; such heightened NO release was also attenuated after in vivo treatment with the SPR blocker. In conclusion, SP plays a direct role in promoting activation of the neutrophil and endothelium as well as induction of NO production; these processes might participate in the oxidative stress that contributes to the depletion of blood glutathione and cardiac pathology.