{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:06:59Z","timestamp":1762898819119},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[1994,5]]},"abstract":"<jats:p>In previous work we reported the elevation of circulating inflammatory cytokines in rodents maintained on a Mg(2+)-deficient diet. Within the first week of Mg2+ deficiency, significant elevation of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) occurs. The present study was designed to assess the effects of SP receptor blockade by CP-96,945 and its inactive enantiomer CP-96,344 on tissue cytokine levels and in vivo oxidative indexes. CP-96,345 had no significant effect on circulating levels of SP or CGRP; however, at the tissue level, a significant decrease (P &lt; .01) in myocardial accumulation of SP occurred; the inactive enantiomer was only slightly effective. In addition, CP-96,345 significantly reduced (by 53%) the accumulation of tumor necrosis factor-alpha (TNF-alpha) (but not interleukin-1 and interleukin-6) within the lesions; the effect of the enantiomer was insignificant. We conclude that treatment with CP-96,345 inhibits SP and TNF-alpha tissue levels in cardiac lesions, indicating a linkage between this neuropeptide and TNF-alpha. Both SP and TNF-alpha can trigger free radical production; plasma thiobarbituric acid-reactive materials were elevated 2.5-fold and red blood cell reduced glutathione was reduced 55% during Mg2+ deficiency. In the presence of CP-96,345, both indexes of in vivo oxidation were significantly attenuated; the enantiomer was ineffective. These latter observations point to a neuropeptide\/TNF-alpha\/free radical-triggered mechanism that may be the major pathway of systemic oxidative injury inducing the cardiomyopathic lesions seen during Mg2+ deficiency.<\/jats:p>","DOI":"10.1161\/01.res.74.5.1009","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"1009-1013","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Blockade of cardiac inflammation in Mg2+ deficiency by substance P receptor inhibition."],"prefix":"10.1161","volume":"74","author":[{"given":"W B","family":"Weglicki","sequence":"first","affiliation":[{"name":"Department of Medicine, George Washington University Medical Center, Washington, DC 20037."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I T","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Medicine, George Washington University Medical Center, Washington, DC 20037."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T M","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Medicine, George Washington University Medical Center, Washington, DC 20037."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/pdf\/10.1161\/01.RES.74.5.1009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:39:55Z","timestamp":1715546395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.74.5.1009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1994,5]]}},"alternative-id":["10.1161\/01.RES.74.5.1009"],"URL":"https:\/\/doi.org\/10.1161\/01.res.74.5.1009","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,5]]},"assertion":[{"value":"1994-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}