Yusoff Nik Syamimi Nik, Mustapha Zulkarnain, Sharif Sharifah Emilia Tuan, Govindasamy Chandran, Sirajudeen Kuttulebbai Nainamohamed Salam
Department of Chemical Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
Department of Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
J Environ Pathol Toxicol Oncol. 2017;36(1):43-53. doi: 10.1615/JEnvironPatholToxicolOncol.2017014521.
Oxidative stress has been suggested to play a role in hypertension- and hypertension-induced organ damage. The effect of antihypertensive drug treatments on oxidative stress markers has not been well assessed. Therefore, in this study we investigated the effect of enalapril on oxidative stress markers in hearts of hypertensive rat models such as spontaneously hypertensive rats (SHR) and SHRs administered N-nitro-L-arginine methyl ester (SHR+L-NAME rats). Male rats were divided into four groups: SHRs, SHR+enalapril (SHR-E) rats, SHR+L-NAME rats, SHR+enalapril+L-NAME (SHRE+L-NAME) rats. Rats (SHREs) were administered enalapril (30 mg kg-1 day-1) in drinking water from week 4 to week 28 and L-NAME (25 mg kg-1 day-1) from week 16 to week 28 in drinking water. At the end of 28 weeks, animals were sacrificed, and their hearts were collected for the assessment of oxidative stress markers and histological examination. Enalapril treatment significantly enhanced the total antioxidant status (TAS) (P < 0.001), reduced the oxidized glutathione ratio (GSH : GSSG) (P < 0.001), and reduced to thibarbituric acid reactive substances (TBARS) (P < 0.001) and protein carbonyl content (PCO) (P < 0.001), which thus reduced the oxidative stress in the heart. The fibrosis areas in SHRs and SHR+L-NAME rats were also markedly reduced. These findings suggest that enalapril might play a protective role in hypertension- and hypertension-induced organ damage.
氧化应激被认为在高血压及高血压所致器官损伤中起作用。抗高血压药物治疗对氧化应激标志物的影响尚未得到充分评估。因此，在本研究中，我们调查了依那普利对高血压大鼠模型（如自发性高血压大鼠（SHR）和给予N-硝基-L-精氨酸甲酯的SHR（SHR+L-NAME大鼠））心脏氧化应激标志物的影响。雄性大鼠分为四组：SHR组、SHR+依那普利（SHR-E）组、SHR+L-NAME组、SHR+依那普利+L-NAME（SHRE+L-NAME）组。从第4周开始至第28周，给大鼠（SHREs）饮用含依那普利（30 mg kg-1 天-1）的水，从第16周开始至第28周饮用含L-NAME（25 mg kg-1 天-1）的水。在28周结束时，处死动物，收集其心脏用于评估氧化应激标志物和进行组织学检查。依那普利治疗显著提高了总抗氧化状态（TAS）（P < 0.001），降低了氧化型谷胱甘肽比率（GSH : GSSG）（P < 0.001），并降低了硫代巴比妥酸反应性物质（TBARS）（P < 0.001）和蛋白质羰基含量（PCO）（P < 0.001），从而减轻了心脏的氧化应激。SHR组和SHR+L-NAME组大鼠的纤维化面积也明显减小。这些发现表明依那普利可能在高血压及高血压所致器官损伤中发挥保护作用。
