{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:16:33Z","timestamp":1761988593898},"reference-count":48,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p> Compelling clinical reports reveal that behavioral stress alone is sufficient to cause reversible myocardial dysfunction in selected individuals. We developed a rodent stress cardiomyopathy model by a combination of prenatal and postnatal behavioral stresses (Stress). We previously reported a decrease in percent fractional shortening by echo, both systolic and diastolic dysfunction by catheter-based hemodynamics, as well as attenuated hemodynamic and inotropic responses to the \u03b2-adrenergic agonist, isoproterenol (ISO) in Stress rats compared with matched controls (Kan H, Birkle D, Jain AC, Failinger C, Xie S, Finkel MS. J Appl Physiol 98: 77\u201382, 2005). We now report enhanced catecholamine responses to behavioral stress, as evidenced by increased circulating plasma levels of norepinephrine ( P &lt; 0.01) and epinephrine ( P &lt; 0.01) in Stress rats vs. controls. Cardiac myocytes isolated from Stress rats also reveal evidence of oxidative stress, as indicated by decreased ATP, increased GSSG, and decreased GSH-to-GSSG ratio in the presence of increased GSH peroxidase and catalase activities ( P &lt; 0.01, for each). We also report blunted inotropic and intracellular Ca<jats:sup>2+<\/jats:sup> concentration responses to extracellular Ca<jats:sup>2+<\/jats:sup> ( P &lt; 0.05), as well as altered inotropic responses to the intracellular calcium regulator, caffeine (20 mM; P &lt; 0.01). Treatment of cardiac myocytes with N-acetylcysteine (NAC) (10<jats:sup>\u22123<\/jats:sup> M) normalized calcium handling in response to ISO and extracellular Ca<jats:sup>2+<\/jats:sup> concentration and inotropic response to caffeine ( P &lt; 0.01, for each). NAC also attenuated the blunted inotropic response to ISO and Ca<jats:sup>2+<\/jats:sup> ( P &lt; 0.01, for each). Surprisingly, NAC did not reverse the changes in GSH, GSSG, or GSH-to-GSSG ratio. These data support a GSH-independent salutary effect of NAC on intracellular calcium signaling in this rodent model of stress-induced cardiomyopathy. <\/jats:p>","DOI":"10.1152\/japplphysiol.01471.2012","type":"journal-article","created":{"date-parts":[[2013,5,31]],"date-time":"2013-05-31T03:02:00Z","timestamp":1369969320000},"page":"514-524","source":"Crossref","is-referenced-by-count":7,"title":["<i>N<\/i>-acetylcysteine reverses cardiac myocyte dysfunction in a rodent model of behavioral stress"],"prefix":"10.1152","volume":"115","author":[{"given":"Fangping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessalyn M.","family":"Hadfield","sequence":"additional","affiliation":[{"name":"Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chalak","family":"Berzingi","sequence":"additional","affiliation":[{"name":"Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Hollander","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane B.","family":"Miller","sequence":"additional","affiliation":[{"name":"National Institute of Occupational Safety and Health, Morgantown, West Virginia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cody E.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Department of Medicine, West Virginia University School of Medicine, Morgantown, West Virginia;"},{"name":"Department of Psychiatry, West Virginia University School of Medicine, Morgantown, West Virginia;"},{"name":"Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, West Virginia;"},{"name":"National Institute of Occupational Safety and Health, Morgantown, West Virginia; and"},{"name":"Louis A. 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