Possible Contribution of Mineralocorticoid Receptor Activation on Glucocorticoid-Induced Left Ventricular Remodeling in Adrenalectomized Rat.
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Date
2013-06
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Abstract
Background: Chronic glucocorticoid treatment induces the development of renal injury via
mineralocorticoid receptor (MR) activation in bilaterally adrenalectomized rats. It has been hypothesized
that glucocorticoid contributes to the development of left ventricular (LV) remodeling through MR
activation in bilaterally adrenalectomized rats (ADX).Methods: ADX rats were maintained with 1%NaCl
in drinking water and randomly treated as follows for 8 weeks: vehicle (n=7), bilateral adrenalectomy
(ADX) + hydrocortisone (HYDRO) (5 mg/kg/day, subcutaneous, n=7), and ADX + HYDRO + eplerenone
(0.125% in chow; approximately 75 mg/kg/day, n=7). An osmotic minipump was implanted
subcutaneously for continuous infusion of HYDRO. Results: As compared with control vehicletreated
uninephrectomized rats, ADX+HYDRO treatment for 8 weeks significantly increased systolic
blood pressure, LV weight, collagen content and mRNA levels of atrial natriuretic peptide, brain
natriuretic peptide, and collagen type 1 and III. These changes were associated with increase in LV
thiobarbituric acid reactive substances content, dihydroethidium fluorescence and mRNA levels of
NADPH oxidase subunits. Treatment with a selective MR antagonist, eplerenone significantly
attenuated HYDRO induced changes in LV parameters. HYDRO-induced increases in mRNA and
protein levels of serum and glucocorticoid-regulated kinases 1 were prevented by eplerenone.
Conclusion: These data suggest that chronic glucocorticoid treatment induces LV tissue remodeling
through MR dependent mechanism in bilateral adrenalectomized rats.
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Keywords
hydrocortisone, mineralocorticoid receptor, eplerenone, LV remodeling.
Citation
Islam Kazi Rafiqul, Sherjee Shamshad J, Mori Hirohito, Kobara Hideki, Nishiyama Noriko, Moitry Nazia F, Nakano Daisuke, Mostofa Mahbub, Nishiyama Akira. Possible Contribution of Mineralocorticoid Receptor Activation on Glucocorticoid-Induced Left Ventricular Remodeling in Adrenalectomized Rat. Journal of Bangladesh Society of Physiologists. 2013 June; 8(1): 6-15.