Sheik Uduman Mohamed Saleem Thattakudian, Reddy Rajitha Bodd, Punuru Priyanka, Chakka Gopinath, Karunakaran Gauthaman
Department of Pharmacology, Annamacharya College of Pharmacy, Rajampet 516126, India.
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia.
Adv Pharmacol Sci. 2016;2016:4608979. doi: 10.1155/2016/4608979. Epub 2016 Mar 6.
The present study was designed to investigate the role of combined administration of Ramipril and Candesartan against in vitro myocardial ischemic reperfusion injury in rat. Male Wistar albino rats were divided into five groups (n = 6) and treated with saline (10 mL/kg), Ramipril (2 mg/kg), Candesartan (1 mg/kg), and the combination of both drugs, respectively 24 h before induction of global ischemia (5 min of stabilization, 9 min of global ischemia, and 12 min of reflow). Combination of Ramipril and Candesartan when compared to the monotherapy significantly increased the levels of superoxide dismutase, reduced glutathione, catalase, and nitric oxide and decreased the levels of thiobarbituric acid reactive substances. In addition, the superior protective role of combination of Ramipril and Candesartan on ischemia induced myocardial damage was further confirmed by well preserved myocardial tissue architecture in light microscopy and transmission electron microscopy analysis studies. The combination was proved to be effective in salvaging the myocardial tissue against ischemic reperfusion injury when compared to the monotherapy of individual drugs and further investigations on protective mechanism of drugs by increasing the nitric oxide level at molecular levels are needed.
本研究旨在探讨雷米普利和坎地沙坦联合给药对大鼠体外心肌缺血再灌注损伤的作用。雄性Wistar白化大鼠分为五组(n = 6),分别在诱导全心缺血(5分钟稳定期、9分钟全心缺血和12分钟再灌注)前24小时用生理盐水(10 mL/kg)、雷米普利(2 mg/kg)、坎地沙坦(1 mg/kg)以及两种药物联合治疗。与单一疗法相比,雷米普利和坎地沙坦联合使用显著提高了超氧化物歧化酶、还原型谷胱甘肽、过氧化氢酶和一氧化氮的水平,并降低了硫代巴比妥酸反应性物质的水平。此外,通过光学显微镜和透射电子显微镜分析研究中保存完好的心肌组织结构,进一步证实了雷米普利和坎地沙坦联合使用对缺血诱导的心肌损伤具有更好的保护作用。与单一药物治疗相比,联合用药被证明在挽救心肌组织免受缺血再灌注损伤方面是有效的,并且需要进一步在分子水平上通过提高一氧化氮水平来研究药物的保护机制。