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...
Objective To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). Methods We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. Results Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1–9.3) than in the control group (4.3 months, 95% CI: 3.6–5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1–16.5; control: 8.5 months, 95% CI: 7.6–9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. Conclusions Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. Key Points • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.
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