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Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: Effects of substance P-receptor inhibition

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Abstract

Dietary deficiency of magnesium (Mg) in rodents results in cardiomyopathic lesion formation. In our rat model, these lesions develop after 3 weeks on the Mg-deficient diet; significant elevation of several cytokines, IL-1, IL-6 and TNFα also occurs. In probing the mechanisms of lesion formation, we obtained data supporting the participation of free radicals (Freedman AMet al.: Bioch Biophys Res Commun 1990; 170: 1102). Recently, we identified an early elevation of circulating substance P and proposed a role of neurogenic peptides during Mg-deficiency (Weglicki WB, Phillips TM: Am J Phys 1992; 262: R734). The present study was designed to evaluate the contribution of neurogenic peptides to the pathogenesis of Mg-deficiency. In the blood, substance-P and calcitonin gene related peptide (CGRP) are elevated during the first week on the diet. During the second week, circulating histamine, PGE2 and TBAR-materials were elevated and red cell glutathione was reduced, all prior to the elevation of the inflammatory cytokines during the third week. When the rats were treated with the substance P-receptor blocker [CP-96,345], the levels of substance P and CGRP remained elevated; however, increases in histamine, PGE2, TBAR-materials, and the decrease in red cell glutathione were inhibited; also, the development of cardiac lesions was inhibited significantly. These data support a central role for neurogenic peptides, especially substance P, in the development of cardiomyopathic lesions during Mg-deficiency.

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Authors and Affiliations

  1. Department of Medicine, George Washington University Medical Center, 20037, Washington, D. C., USA

    W. B. Weglicki, I. T. Mak, R. E. Stafford, B. F. Dickens & T. M. Phillips

  2. Department of Physiology, George Washington University Medical Center, 2300 Eye St., 20037, Washington, D. C., USA

    W. B. Weglicki, I. T. Mak, B. F. Dickens & M. M. Cassidy

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  1. W. B. Weglicki
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  2. I. T. Mak
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  3. R. E. Stafford
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  4. B. F. Dickens
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  5. M. M. Cassidy
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  6. T. M. Phillips
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Weglicki, W.B., Mak, I.T., Stafford, R.E. et al. Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: Effects of substance P-receptor inhibition. Mol Cell Biochem 130, 103–109 (1994). https://doi.org/10.1007/BF01457391

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  • DOI: https://doi.org/10.1007/BF01457391

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