N-acetylcysteine reverses cardiac myocyte dysfunction in a rodent model of behavioral stress

Details

• Personal Author:
  Berzingi C ; Chen F ; Finkel M ; Hadfield J ; Hollander J ; Miller D ; Nichole C
• Description:
  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 pre-natal and post-natal behavioral stresses (Stress). We previously reported a decrease in % FS by echo, both systolic and diastolic dysfunction by catheter-based hemodynamics, as well as attenuated hemodynamic and inotropic responses to the beta adrenergic agonist, isoproterenol (ISO) in Stress compared with matched Controls. We now report enhanced catecholamine responses to behavioral stress as evidenced by increased circulating plasma levels of norepinephrine (p<0.01) and epinephrine (p<0.01) in Stress vs Controls. Cardiac myocytes isolated from Stress also reveal evidence of oxidative stress as indicated by decreased ATP, increased GSSG and decreased GSH/GSSG ratio in the presence of increased glutathione peroxidase (GPX) and catalase activities (p<0.01, for each). We also report blunted inotropic and [Ca2+]i responses to extracellular Ca2+ ([Ca2+]out; p<0.05) as well as altered inotropic responses to the intracellular calcium regulator, caffeine (20mM; p<0.01). Treatment of cardiac myocytes with NAC (10-3 M) normalized calcium handling in response to ISO and [Ca2+]out and inotropic response to caffeine (p<0.01, for each). NAC also attenuated the blunted inotropic response to ISO and Ca2+ (p<0.01, for each). Surprisingly, NAC did not reverse the changes in GSH, GSSG or GSH/GSSG ratio. These data support a glutathione-independent salutary effect of NAC on intracellular calcium signaling in this rodent model of stress-induced cardiomyopathy. [Description provided by NIOSH]
• Subjects:
  Behavior Blood Calcium Compounds Cardiovascular Diseases Cardiovascular System Laboratories Musculoskeletal Diseases Musculoskeletal System Occupational Health Safety
• Keywords:
  Analytical-models Author Keywords: Prenatal Stress Calcium-compounds Cardiac-function Cardiovascular-function Cardiovascular-system-disorders Catecholamines Cellular-function Cellular-reactions Heart Heart Function Hemodynamics Laboratory-animals Laboratory-testing Muscle-cells Muscle-stress Myocardial-disorders Myocardium N-acetylcysteine Oxidative-processes Peroxidases Physiological-stress Prenatal-exposure Stress Systolic-pressure

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• ISSN:
  8750-7587
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  115
• Issue:
  4
• NIOSHTIC Number:
  nn:20043022
• Citation:
  J Appl Physiol 2013 Aug; 115(4):514-524
• Contact Point Address:
  Mitchell S. Finkel, M.D., Professor and Associate Chairman, Department of Medicine, WVU Cardiology, Medical Center Drive, Morgantown, WV 26506-9157
• Email:
  mfinkel@hsc.wvu.edu
• CAS Registry Number:
  (-)-Epinephrine (CAS RN 51-43-4) ; Caffeine (CAS RN 58-08-2) ; Calcium (CAS RN 7440-70-2) ; Glutathione (CAS RN 70-18-8) ; Isoproterenol (CAS RN 7683-59-2) ; N-Acetyl-L-cysteine (CAS RN 616-91-1)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Healthcare and Social Assistance ; Transportation, Warehousing and Utilities
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Applied Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:99a5feff61b780821cf4e0ee485c6d098637b9adc666228f47b61ddd0fdeeb415a68c200085460831abe21343734ac777f06d8c6bb78776b4c4eedcc9e19368b
• Download URL:
  https://stacks.cdc.gov/view/cdc/195053/cdc_195053_DS1.pdf
• File Type:
  [PDF - 784.76 KB ]