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.Keywords: angiotensin-(1-7); Mas; angiotensin I receptor; angiotensin II receptor; adriamycin; heart failure; telmisartan; losartan Acta Pharmacologica Sinica (2011Sinica ( ) 32: 1345Sinica ( -1350 doi: 10.1038/aps.2011 published online 3 Oct 2011 Original Article # The first two authors contributed equally to this work. * To whom correspondence should be addressed. npg an oncogene as well as a receptor for Ang-(1-7) [13] . In a previous work, Mas receptor-deficient mice showed higher blood pressure values, impaired endothelial function, decreased NO production and lower endothelial NO synthetase expression [14] , indicating that the Ang-(1-7)/Mas receptor axis plays an important role in cardioprotective and antihypertensive effects. Importantly, Ang-(1-7) can prevent heart failure after myocardial ischemia [15] . Some recent studies have reported that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two classes of drugs that target RAS, may prevent ADR-induced cardiotoxicity [16][17][18][19] . However, the underlying mechanisms are largely unclear. In the present study, we investigated the regulation of two ARBs (telmisartan and losartan) on plasma Ang-(1-7) levels and the mRNA and protein expression of the myocardial AT 1 R, AT 2 R and Mas receptors in ADR-induced heart failure. Materials and methods Animals Experimental protocolRats were randomly divided into four groups: (1) the control group (n=10, intraperitoneally injected an...
Auto-antibodies against to angiotensin II type 1 receptor (AT 1 R-AA) have been discovered in patients with hypertension and they have a close relationship with inflammatory factors. However, auto-antibodies to angiotensin II type 2 receptor (AT 2 R-AA) are seldom investigated in hypertension. Subjects (n ¼ 138) were enrolled and divided into three groups according to their blood pressure levels by using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) criteria: normotensive (≤120/80 mmHg, n ¼ 31), prehypertensive (120-139/80-89 mmHg, n ¼ 39), and hypertensive (≥140/90 mmHg, n ¼ 68) groups. Plasma AT 1 R-AAs and AT 2 R-AAs were detected by enzyme-linked immunosorbent assay. Plasma tumour necrosis factor-a (TNF-a), endothelin-1 (ET-1), and angiotensin II (Ang II) were measured by radioimmunity assay. (i) Plasma AT 1 R-AAs were positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), TNF-a, ET-1, and Ang II. (ii) AT 2 R-AAs were negatively correlated with SBP, DBP, MAP, TNF-a, ET-1, Ang II, as well as uric acid and serum creatinine. (iii) TNF-a, ET-1, Ang II (all P , 0.01, when compared with the normotensive group), blood uric acid, and serum creatinine (both P , 0.05, when compared with the normotensive group) increased with BP level. (iv) Multiple linear regression analyses showed that age, AT 1 R-AAs, AT 2 R-AAs, and ET-1 were independent predictors for SBP. AT 1 R-AAs, AT 2 R-AAs, and ET-1 were independent predictors for DBP. AT 1 R-AAs, AT 2 RAAs, ET-1, and Ang II were independent predictors for MAP. Plasma AT 1 R-AAs and AT 2 RAAs play an important role in hypertension progression. AT 2 R-AAs are inversely related to renal dysfunction.
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