NEUROGENIC PEPTIDES AND THE CARDIOMYOPATHY OF MAGNESIUM-DEFICIENCY - EFFECTS OF SUBSTANCE P-RECEPTOR INHIBITION

Dietary deficiency of magnesium (Mg) in rodents results in cardiomyopa thic lesion formation. In our rat model, these lesions develop after 3 weeks on the Mg-deficient diet; significant elevation of several cyto kines, 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 sub stance P and proposed a role of neurogenic peptides during Mg-deficien cy (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 c alcitonin gene related peptide (CGRP) are elevated during the first we ek on the diet. During the second week, circulating histamine, PGE(2) and TBAR-materials were elevated and red cell glutathione was reduced, all prior to the elevation of the inflammatory cytokines during the t hird week. When the rats were treated with the substance P-receptor bl ocker [CP-96,345], the levels of substance P and CGRP remained elevate d; however, increases in histamine, PGE(2), TBAR-materials, and the de crease in red cell glutathione were inhibited; also, the development o f cardiac lesions was inhibited significantly. These data support a ce ntral role for neurogenic peptides, especially substance P, in the dev elopment of cardiomyopathic lesions during Mg-deficiency.