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

Mol Cell Biochem. 1994 Jan 26;130(2):103-9. doi: 10.1007/BF01457391.


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 TNF alpha also occurs. In probing the mechanisms of lesion formation, we obtained data supporting the participation of free radicals (Freedman AM et 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biphenyl Compounds / pharmacology*
  • Cardiomyopathies / etiology
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / physiopathology*
  • Cytokines / biosynthesis
  • Magnesium Deficiency / complications*
  • Neurokinin-1 Receptor Antagonists*
  • Neuropeptides / physiology*
  • Rats
  • Rats, Sprague-Dawley


  • Biphenyl Compounds
  • Cytokines
  • Neurokinin-1 Receptor Antagonists
  • Neuropeptides
  • CP 96345