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

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 (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 (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, 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 AT1R. Treatment with telmisartan and losartan effectively increased the plasma level of Ang-(1–7) and suppressed myocardial AT1R expression, but did not influence the expression of Mas receptor and AT₂R.

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 AT1R expression.