Oxidative stress and calcium/calmodulin-dependent protein kinase II contribute to the development of sustained β adrenergic receptor-stimulated cardiac hypertrophy in rats / 生理学报

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.

Damage effects of sleep deprivation on myocardium and its antioxygen index in rats / 中国应用生理学杂志

<p><b>AIM</b>To explore the effects of sleep deprivation (SD) on myocardium and its antioxygen index.</p><p><b>METHODS</b>35 Sprague Dawley rats were randomly divided into five groups: Cage control, Tank control, SD 2 d, SD 4 d and SD 6 d. The "flower pot" technique was used to establish rats sleep deprivation model followed by record of surface electrocardiogram, detection of myocardium morphology changes under microscope and transmission electron microscope and investigation of MDA content and SOD activity of myocardial mitochondria.</p><p><b>RESULTS</b>After sleep deprivation, heart rate increased and ECG showed ischemia of myocardium; subcellular organelles such as chromosome, endoplasmic reticulum, mitochondria, intercalated disk impaired, myofibril lysis or necrosis, and lipid peroxidation reaction effects spread widely; edema, bleeding of the microvessels and invasion of the monocytes could be seen in the lumen. The MDA level increased and SOD activity increased followed by a decreased trend.</p><p><b>CONCLUSION</b>Sleep deprivation can induce damage on myocardium, and the stress especially oxygen stress caused by SD may be the possible mechanism.</p>