title: Excess of glucocorticoid induces cardiac dysfunction via activating angiotensin II pathway.
abstract: BACKGROUND
  Glucocorticoid is widely used as an anti-inflammatory drug in various diseases however excess of it often causes cardiovascular complications. The present study was undertaken to understand the molecular mechanism of glucocorticoid-induced cardiac dysfunction.
  
  
  METHODS
  Rats were treated daily with synthetic glucocorticoid, dexamethasone with or without mifepristone or losartan up to 15 days. Hemodynamic parameters were measured by PV-loop method using Millar's instrument. Cardiac remodelling, fibrosis and oxidative stress were monitored after 15 days.
  
  
  RESULTS
  The systolic blood pressure was increased whereas the heart beat and cardiac output (n=6) were decreased by dexamethasone. Dexamethasone caused increase in the heart weight to body weight ratio (P<0.001, n=20), increased level of mRNA of atrial natriuretic peptide and an increased deposition of collagens in the extracellular matrix of the left ventricle which were inhibited by both mifepristone and losartan. The rate of oxygen consumption was decreased in association with increased levels of hypoxia inducible factor 1alpha, lipid peroxidation (P<0.01, n=3) and superoxide dismutase activity (P<0.01, n=3) in dexamethasone treated rat heart. All these changes were reversed by mifepristone and losartan.
  
  
  CONCLUSIONS
  The excess of glucocorticoid induces cardiac remodelling and pathophysiolgical changes of the myocardium via angiotensin II signalling pathway.
authors: Molecular Endocrinology Laboratory, Indian Institute of Chemical Biology, Kolkata, India.
authors: Sreerupa Ghose
authors: SG
authors: Roy
authors: Priyanka
authors: P
authors: De
authors: Debasri
authors: D
authors: Mukherjee
authors: Vivek
authors: V
authors: Chander
authors: Aditya
authors: A
authors: Konar
authors: Debasish
authors: D
authors: Bandyopadhyay
authors: Arun
authors: A
authors: Bandyopadhyay
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044140:Receptor, Angiotensin, Type 1; C472610:atrial natriuretic peptide, rat; D000804:Angiotensin II; D003907:Dexamethasone; D009320:Atrial Natriuretic Factor; D003094:Collagen; D013482:Superoxide Dismutase