Excess of glucocorticoid induces cardiac dysfunction via activating angiotensin II pathway.
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.
Roy
Sreerupa Ghose
SG
Molecular Endocrinology Laboratory, Indian Institute of Chemical Biology, Kolkata, India.
De
Priyanka
P
Mukherjee
Debasri
D
Chander
Vivek
V
Konar
Aditya
A
Bandyopadhyay
Debasish
D
Bandyopadhyay
Arun
A
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
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