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. 2011 Nov;32(11):1345-50.
doi: 10.1038/aps.2011.96. Epub 2011 Oct 3.

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

Wen-na Zong  1 , Xiao-hui Yang, Xiu-mei Chen, Hong-juan Huang, Hong-jian Zheng, Xiao-yi Qin, Yong-hong Yong, Kejiang Cao, Jun Huang, Xin-zheng Lu
Affiliations

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

Wen-na Zong et al. Acta Pharmacol Sin. 2011 Nov.

Abstract

Aim: To investigate the possible effects of telmisartan and losartan 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 (AT(1)R / AT(2)R) 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 (Tel+ADR) and losartan plus ADR-treated group (Los+ADR). ADR was administrated (2.5 mg/kg, ip, 6 times in 2 weeks). The rats in the Tel+ADR and Los+ADR groups were treated orally with telmisartan (10 mg/kg daily po) and losartan (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, AT(1)R and AT(2)R 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 AT(2)R, while significantly increased the expression of myocardial AT(1)R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1-7) and suppressed myocardial AT(1)R expression, but did not influence the expression of Mas receptor and AT(2)R.

Conclusion: The protective effects of telmisartan and losartan in ADR-induced heart failure may be partially due to regulation of circulating Ang-(1-7) and myocardial AT(1)R expression.

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Figures

Figure 1
Figure 1
Changes in body weight in each group of rats. Controls=With normal saline injection; ADR-HF=Adriamycin-induced heart failure rats; Tel+ADR=Telmisartan plus Adriamycin-treated rats; Los+ADR=Losartan plus Adriamycin-treated rats. Data are expressed as mean±SD. bP<0.05, cP<0.01 vs control group. fP<0.01 vs ADR-HF group. Control, n=10; ADR-HF, n=9; Tel+ADR, n=12; and Los+ADR, n=13.
Figure 2
Figure 2
Transthoracic echocardiography to evaluate the cardiac function of rats. Controls=With normal saline injection; ADR-HF=Adriamycin-induced heart failure rats; Tel+ADR=Telmisartan plus Adriamycin-treated rats; Los+ADR=Losartan plus Adriamycin-treated rats.
Figure 3
Figure 3
Plasma levels of angiotensin-(1–7) [Ang-(1–7)] were determined by ELISA in rats of the control, ADR-HF, Tel+ADR, and Los+ADR groups at the end of the study. Controls=With normal saline injection; ADR-HF=Adriamycin-induced heart failure rats; Tel+ADR=Telmisartan plus Adriamycin-treated rats; Los+ADR=Losartan plus Adriamycin-treated rats. Mean±SD. bP<0.05, cP<0.01 vs controls. eP<0.05 vs ADR-HF.
Figure 4
Figure 4
The mRNA expression levels of the Mas receptor (A), AT1R (B), and AT2R (C) in cardiac tissues at the end of the study were determined by RT-PCR. The amounts are expressed relative to the amount of β-actin. Controls=With normal saline injection; ADR-HF=Adriamycin-induced heart failure rats; Tel+ADR=Telmisartan plus Adriamycin-treated rats; Los+ADR=Losartan plus Adriamycin-treated rats. n=6. Mean±SD. bP<0.05, cP<0.01 vs control groups. fP<0.01 vs ADR-HF.
Figure 5
Figure 5
The protein expression levels of the Mas receptor (A), AT1R (B), and AT2R (C) in cardiac tissues at the end of the study were determined by Western blotting. Amounts of Mas, AT1R, and AT2R were expressed relative to the amount of GAPDH in each sample. Controls=With normal saline injection; ADR-HF=Adriamycin-induced heart failure rats; Tel+ADR=Telmisartan plus Adriamycin-treated rats; Los+ADR=Losartan plus Adriamycin- treated rats. Data are expressed as mean±SD. bP<0.05, cP<0.01 vs control group. fP<0.01 vs ADR-HF.
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