Soner Burak Cem, Sahin Ayşe Saide
Department of Medical Pharmacology, Meram Medical Faculty, Necmettin Erbakan University, Konya 42080, Turkey.
Exp Ther Med. 2014 Nov;8(5):1660-1664. doi: 10.3892/etm.2014.1956. Epub 2014 Sep 11.
Oxidative stress has been implicated in the pathophysiology of several types of cardiovascular disease (CVD). Statins are widely used to inhibit the progression of atherosclerosis and reduce the incidence of CVD. Certain over-the-counter products, including resveratrol, show similar effects to statins and may thus be used in conjunction with statins for the treatment of the majority of patients with CVD. The aim of the present study was to evaluate the effects of atorvastatin, resveratrol and resveratrol + atorvastatin (R+A) pretreatment on myocardial contractions and vascular endothelial functions in the presence of HO as an experimental model of oxidative stress in rats. Four groups were established and referred to as the control, atorvastatin, resveratrol and R+A groups. Atorvastatin (40 mg/kg, per oral) and/or resveratrol (30 mg/kg, intraperitoneal) treatments were administered for 14 days. On the 15th day, the thoracic aortas and hearts of the rats were dissected and placed into isolated organ baths. Vascular responses to cumulative doses of HO (1×10-1×10 M HO) with and without N (G)-nitro-L-arginine methyl ester (L-NAME) incubation were measured. In addition, myocardial electrical stimulation (ES) responses to various HO concentrations (1×10-1×10 M HO) were evaluated. In the control and atorvastatin groups, HO application caused a significant dose-dependent decrease in the ES-induced contractions in the myocardial tissue of rats. In the resveratrol and R+A groups, HO application did not significantly affect myocardial contraction at any dose. In all groups, incubation with L-NAME caused a significant augmentation in the HO response, revealing that this effect was mediated via the vascular endothelium. In conclusion, pretreatment with R+A for CVD appears to be superior to pretreatment with either agent alone.
氧化应激与多种心血管疾病（CVD）的病理生理学有关。他汀类药物被广泛用于抑制动脉粥样硬化的进展并降低CVD的发病率。某些非处方产品，包括白藜芦醇，显示出与他汀类药物相似的效果，因此可与他汀类药物联合用于治疗大多数CVD患者。本研究的目的是在作为大鼠氧化应激实验模型的HO存在下，评估阿托伐他汀、白藜芦醇和白藜芦醇+阿托伐他汀（R+A）预处理对心肌收缩和血管内皮功能的影响。建立了四组，分别称为对照组、阿托伐他汀组、白藜芦醇组和R+A组。给予阿托伐他汀（40mg/kg，口服）和/或白藜芦醇（30mg/kg，腹腔注射）治疗14天。在第15天，解剖大鼠的胸主动脉和心脏并置于离体器官浴中。测量在有和没有N（G）-硝基-L-精氨酸甲酯（L-NAME）孵育的情况下，血管对累积剂量的HO（1×10 - 1×10 M HO）的反应。此外，评估心肌电刺激（ES）对各种HO浓度（1×10 - 1×10 M HO）的反应。在对照组和阿托伐他汀组中，应用HO导致大鼠心肌组织中ES诱导的收缩显著剂量依赖性降低。在白藜芦醇组和R+A组中，任何剂量的HO应用均未显著影响心肌收缩。在所有组中，与L-NAME孵育导致HO反应显著增强，表明这种效应是通过血管内皮介导的。总之，CVD的R+A预处理似乎优于单独使用任何一种药物的预处理。
