Regulation of angiotensin-（1-7） and angiotensin II type 1 receptor by telmisartan and Iosartan in adriamycin-induced rat heart failure

• Published in: 中国药理学报：英文版 2011, Vol.32 (11), p.1345-1350
• Main Author: Wen-na ZONG Xiao-hui YANG Xiu-mei CHEN Hong-juan HUANG Hong-jian ZHENG Xiao-yi QIN Yong-hong YONG Ke- jiang CAO Jun HUANG Xin-zheng LU
• Format: Article
• Language: English
• Subjects: SD大鼠; 受体; 心脏功能; 替米沙坦; 血管紧张素; 衰竭; 诱导; 阿霉素
• ISSN: 1671-4083; 1745-7254

Aim： To investigate the possible effects of telmisartan and Iosartan on cardiac function in adriamycin （ADR）-induced heart failure in rats, and to explore the changes in plasma level of angiotensin-（1-7）[Ang-（1-7）] and myocardial expression of angiotensin II type 1/2 receptors （AT1R / AT2R） and Mas receptor caused by the two drugs. Methods： Male Sprague-Dawley rats were randomly divided into 4 groups： the control group, ADR-treated heart failure group （ADR-HF） telmisartan plus ADR-treated group （TeI＋ADR） and Iosartan plus ADR-treated group （Los＋ADR）. ADR was administrated （2.5 mg/kg, ip 6 times in 2 weeks）. The rats in the TeI＋ADR and Los＋ADR groups were treated orally with telmisartan （10 mg/kg daily po） and Iosartan （30 mg/kg daily）, respectively, for 6 weeks. The plasma level of Ang-（1-7） was determined using ELISA. The mRNA and protein expression of myocardial Mas receptor, AT1R and AT2R were measured using RT-PCR and Western blotting, respectively. Results： ADR significantly reduced the plasma level of Ang-（1-7） and the expression of myocardial Mas receptor and myocardial AT2R, while significantly increased the expression of myocardial AT2R. Treatment with telmisartan and Iosartan effectively increased the plasma level of An8-（1-7） and suppressed myocardial ATIR expression, but did not influence the expression of Mas receptor and AT2R Conclusion： The protective effects of telmisartan and Iosartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-（1-7） and myocardial ATCR expression.