Effect of aliskiren and carvedilol on expression of Ca(2+)/calmodulin-dependent protein kinase II δ-subunit isoforms in cardiac hypertrophy rat model.

Abstract:

CONTEXT:The critical role of CaMKIIδ isoforms in cardiac hypertrophy is well documented. OBJECTIVE:This study was aimed to investigate the possible inhibitory effects of aliskiren (ALS) and/or carvedilol (CAV) on CaMKIIδ isoforms expression in experimental cardiac hypertrophy. MATERIALS AND METHODS:Male Wistar albino rats were subcutaneously injected with isoproterenol (ISO) (5 mg/kg/day) for 4 weeks to induce cardiac hypertrophy. Hypertrophied rats were daily treated with either ALS (10 mg/kg) and/or CAV (10 mg/kg). At the end of the treatment, rats were killed; blood and hearts were collected for assessing different biochemical parameters. RESULTS:ISO treatment significantly increased heart weight to body weight (HW/BW) ratio, serum creatine kinase MB (CK-MB) and troponin T (Tn-T) levels, and plasma renin activity (PRA) as compared to control rats. Additionally, ISO treatment produced a significant increase in the expression of myocardial CaMKIIδ2 and CaMKIIδ3 that were associated with significant elevation in myocardial caspase-3 protein expression. Histopathological examination of rats exposed to ISO treatment showed severe myocardial cell degeneration. ALS and/or CAV treatment significantly reduced the altered HW/BW ratio, serum CK-MB and Tn-T levels, PRA, and caspase-3 protein expression in hypertrophied rats, with maximal improvement in the combination group. These biochemical findings were supported by the histopathological examination of the heart tissue. Additionally, treatment with ALS and CAV significantly inhibited ISO-induced increase in CaMKIIδ2 and CaMKIIδ3 expression levels. DISCUSSION AND CONCLUSION:The present study indicated that ALS and CAV treatment ameliorated ISO-induced hypertrophy via inhibiting the expression and the activity of CaMKIIδ isoforms and the associated myocardial apoptosis.

journal_name

Toxicol Mech Methods

authors

Bin-Dayel AF,Abdel Baky NA,Fadda LM,Mohammad RA,Al-Mohanna F

doi

10.3109/15376516.2015.1128035

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

122-31

issue

2

eissn

1537-6516

issn

1537-6524

journal_volume

26

pub_type

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