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阿利吉仑、替米沙坦和托塞米对 l-硝基精氨酸甲酯(l-NAME)诱导的高血压大鼠心功能障碍的影响。

Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME) induced hypertension in rats.

机构信息

Department of Pharmacology, Faculty of Medicine, Fayoum University, Egypt.

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Egypt.

出版信息

J Adv Res. 2015 Nov;6(6):967-74. doi: 10.1016/j.jare.2014.11.003. Epub 2014 Nov 20.

Abstract

Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME) induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2 (-)/NO3 (-). After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure.

摘要

本研究旨在比较阿利吉仑、替米沙坦和托塞米对 l-硝基精氨酸甲酯(l-NAME)诱导的高血压大鼠的心脏保护作用。三种药物与 l-NAME 同时每日给药 8 周,每种药物和 l-NAME 均设立对照组。通过每两周测量一次动物的收缩压和心率来评估保护程度。实验结束时采集血液样本,用于估计 NO2 (-)/NO3 (-)水平。然后处死动物进行心脏解剖,以检测胶原 I 和 III 基因表达。进行组织病理学研究以评估胶原沉积的程度。研究结果表明,与 l-NAME 相比,三种药物均能显著降低血压。阿利吉仑和替米沙坦在所有测量指标上均无显著差异,但与托塞米相比,从第 4 周开始,阿利吉仑和替米沙坦治疗组的测量指标均显著降低。在整个实验过程中,三种 l-NAME 治疗组的脉搏率值无明显变化。与 l-NAME 相比,三种药物均能显著增加 NO。三种药物均能显著降低胶原 I 和 III 基因表达,但与 l-NAME 相比,替米沙坦的抑制率最高。比较心脏纤维化的抑制百分比,替米沙坦和托塞米治疗组之间无显著差异,而两者均优于阿利吉仑。总之,需要进一步的实验研究来阐明阿利吉仑、替米沙坦和托塞米的潜在心脏保护机制,并评估它们在心力衰竭治疗中的疗效。

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