Oxidative stress and calcium/calmodulin-dependent protein kinase II contribute to the development of sustained β adrenergic receptor-stimulated cardiac hypertrophy in rats.
- Author:
Yan-Li LIU
1
;
Ben LIU
;
Yang-Yang QU
;
Hui-Juan CHAI
;
Rui LI
;
Ling ZHANG
Author Information
1. Department of Physiology and Pathophysiology, Basic Medical School, Tianjin Medical University, China.
- Publication Type:Journal Article
- MeSH:
Acetylcysteine;
pharmacology;
Animals;
Calcium-Calmodulin-Dependent Protein Kinase Type 2;
metabolism;
Cardiomegaly;
physiopathology;
Isoproterenol;
pharmacology;
Male;
Mitochondria, Heart;
metabolism;
Myocardium;
pathology;
NADPH Oxidase 4;
NADPH Oxidases;
metabolism;
Oxidative Stress;
Rats;
Rats, Wistar;
Reactive Oxygen Species;
metabolism;
Receptors, Adrenergic, beta;
metabolism
- From:
Acta Physiologica Sinica
2013;65(1):1-7
- CountryChina
- Language:Chinese
-
Abstract:
Sustained activation of β adrenergic receptor (βAR) leads to pathologic cardiac hypertrophy. However, the related mechanisms still remain unclear. In this study, we observe how N-acetylcysteine (NAC) affects the oxidative stress and calcium/calmodulin-dependent protein kinase II (CaMKII) expression in heart of isoproterenol (ISO)-stimulated rats, and investigate whether oxidative stress and CaMKII contribute to the development of sustained βAR-stimulated cardiac hypertrophy. Healthy male Wistar rats were randomly separated into 4 groups: control (CTRL), ISO-treated (ISO), control with NAC supplement (CTRL+NAC) and ISO-treated with NAC supplement (ISO+NAC) groups (6 rats in each group). Systolic blood pressure (SBP) was measured in awake rats with the tail-cuff method every week for two weeks. Heart weight/body weight ratio (HW/BW) and HE staining were used for the detection of myocardial hypertrophy. Myocardial mitochondrial reactive oxygen species (ROS) levels were measured by DCF fluorometry. The expressions of activated-CaMKII (p-CaMKII/CaMKII) and NADPH oxidase 4 (NOX(4)) were determined by Western blot analysis. The results showed that ISO-treated (i.p., daily 3 mg/kg, 2 weeks) rats developed an obvious cardiac hypertrophy as expressed by increases of HW/BW and myocyte cross-section area. Cardiac mitochondrial ROS level was significantly enhanced in ISO group as compared to CTRL group (P < 0.05). The expressions of NOX(4) and p-CaMKII in ISO group were also up-regulated as compared to CTRL group (1.4 and 1.6 times of CTRL, respectively, P < 0.05). NAC supplement significantly suppressed the hypertrophic development of heart in ISO-stimulated rats. The cardiac mitochondrial ROS level showed a significant decrease in rats of ISO+NAC group (P < 0.05 vs ISO). In accordance with this, ISO+NAC group rats also showed marked reductions in the expressions of NOX(4) and p-CaMKII/CaMKII compared to ISO group rats (P < 0.05). There were no significant differences of the detected indices between the rats from CTRL+NAC and CTRL groups. SBP showed no differences among four groups. These results suggest that both oxidative stress and CaMKII play important roles in sustained βAR-stimulated cardiac hypertrophy. NAC may suppress ISO-induced cardiac hypertrophy by down-regulating the expression of activated-CaMKII, and by reducing the level of oxidative stress originated from mitochondria and NADPH oxidase pathways.
