Cardioprotective Effects of Telmisartan against Heart Failure in Rats Induced By Experimental Autoimmune Myocarditis through the Modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor Axis
نویسندگان
چکیده
Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan, a well-known angiotensin receptor blockers (ARBs) against experimental autoimmune myocarditis (EAM). EAM was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with telmisartan (10 mg/kg/day) or vehicle for 21 days. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Telmisartan lowered myocardial protein expressions of NADPH oxidase subunits 3-nitrotyrosine, p47phox, p67 phox, Nox-4 and superoxide production significantly than vehicle-treated rats. In contrast myocardial protein levels of ACE-2, ANG 1-7 mas receptor were upregulated in the telmisartan treated group compared with those of vehicle-treated rats. The myocardial protein expression levels of tumor necrosis factor receptor (TNFR)-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78 were decreased in the telmisartan treated rats compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly decreased the protein expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho (MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, telmisartan significantly decreased the production of proinflammatory cytokines, myocardial apoptotic markers and caspase-3 positive cells compared with those of vehicle-treated rats. Therefore, we suggest that telmisartan was beneficial protection against heart failure in rats, at least in part by suppressing inflammation, oxidative stress, ER stress as well as signaling pathways through the modulation of ACE2/ANG1-7/Mas receptor axis.
منابع مشابه
The effect of progressive aerobic continuous training on angiotensin-1, angiotensin-2 and angiotensin-converting enzyme type 2 in patients with heart failure
Background: Chronic hypertension causes structural and functional changes in the heart, ultimately leading to heart failure (HF), which further increases mortality and morbidit. HF is a complex clinical syndrome caused by various structural or functional abnormalities of the heart that impair the filling capacity of the ventricles. The findings of various trials have shown the association betwe...
متن کاملThe pivotal link between ACE2 deficiency and SARS-CoV-2 infection
Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type2 pneumocytes and macrophages), kidney, testisand brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a s...
متن کاملRenoprotection by Telmisartan versus Benazepril in Streptozotocin Induced Diabetic Nephropathy
Diabetic nephropathy (DN) is one of the major causes of end stage renal disease. Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) are preferred for delaying progression of DN. This study compared the preventive renal effects of telmisartan (10 mg/kg, p.o.), an ARB that completely blocks angiotensin action, and benazepril (5 mg/kg, p.o.), an ACE inhibitor, whi...
متن کاملThe effects of Mas receptor antagonist (A779) and renal perfusion pressure on serum nitrite concentration in male and female rats when angiotensin II receptors 1 & 2 were blocked
Introduction: Renin angiotensin system has an important role in blood pressure and renal functions. Active angiotensin-converting enzyme 2 converts angiotensin I into angiotensin-(1-7) which is a vasodilator hormone and interacts with nitric oxide changes as well as other angiotensin II receptors. In this study we evaluated the role of Mas receptor antagonist (A779) and renal perfusion press...
متن کاملRenal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy
Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced...
متن کامل