Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: effects of substance P-receptor inhibition.
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.
Weglicki
W B
WB
Department of Medicine, George Washington University Medical Center, Washington, D.C. 20037.
Mak
I T
IT
Stafford
R E
RE
Dickens
B F
BF
Cassidy
M M
MM
Phillips
T M
TM
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D016207:Cytokines / Q000096:biosynthesis; D008275:Magnesium Deficiency / Q000150:complications*; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001713:Biphenyl Compounds; D016207:Cytokines; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides; C066892:CP 96345