Journal article
Effect of U50,488H, a kappa-opioid receptor agonist on myocardial alpha- and beta-myosin heavy chain expression and oxidative stress associated with isoproterenol-induced cardiac hypertrophy in rat
Molecular and cellular biochemistry, Vol.345(1-2), pp.231-240
12/01/2010
DOI: 10.1007/s11010-010-0577-4
PMID: 20730476
Abstract
Both oxidative stress and beta-MHC expression are associated with pathological cardiac hypertrophy. beta-adrenergic receptor stimulation plays an important role in cardiac hypertrophy. Recent studies have reported a negative interplay between opioid receptors and adrenoceptors in heart. This study investigated the effect of U50,488H (a selective kappa-opioid receptor agonist) on myocardial oxidative stress and alpha- and beta-MHC expression in isoproterenol-induced cardiac hypertrophy. Male Wistar rats were administered normal saline (control), isoproterenol (ISO) (5 mg/kg BW s.c. OD), and isoproterenol with U50,488H (0.4 and 0.6 mg/kg BW, i.p. OD) for 14 days. In a separate group, nor-binaltorphimine (nor-BNI) (0.5 mg/kg, BW, i.p.) (kappa-receptor antagonist) was administered along with ISO and U50,488H. ISO administration caused significant increase in left ventricular (LV) wall thicknesses, LV mass in echocardiography, heart weight to body weight ratio, and myocyte size as compared to control. Both the doses of U50,488H offered significant protection against these changes. The higher dose of U50,488H significantly prevented ISO-induced increase in myocardial lipid peroxidation and depletion of myocardial antioxidants (glutathione, superoxide dismutase, and catalase), while a similar trend (although not significant) was observed with the lower dose also. ISO-induced myocardial fibrosis was also significantly attenuated by both the doses of U50,488H. Isoproterenol-induced beta-MHC expression in the hypertrophied heart was not altered by either doses of U50,488H, however, the latter prevented the loss of myocardial alpha-MHC expression. All these effects of U50,488H were blocked by nor-BNI. This study provides the evidence that U50,488H reduced oxidative stress and preserved expression of alpha-MHC in isoproterenol-induced cardiac hypertrophy.
Details
- Title: Subtitle
- Effect of U50,488H, a kappa-opioid receptor agonist on myocardial alpha- and beta-myosin heavy chain expression and oxidative stress associated with isoproterenol-induced cardiac hypertrophy in rat
- Creators
- Amardeep Jaiswal - All India Institute of Medical SciencesSantosh Kumar - All India Institute of Medical SciencesSandeep Seth - All India Institute of Medical SciencesAmit Kumar Dinda - All India Institute of Medical SciencesSubir Kumar Maulik - All India Institute of Medical Sciences
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biochemistry, Vol.345(1-2), pp.231-240
- Publisher
- Springer Nature
- DOI
- 10.1007/s11010-010-0577-4
- PMID
- 20730476
- ISSN
- 0300-8177
- eISSN
- 1573-4919
- Number of pages
- 10
- Grant note
- Indian council of Medical Research, New Delhi, India; Indian Council of Medical Research (ICMR)
- Language
- English
- Date published
- 12/01/2010
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359790302771
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