Telmisartan acts through the modulation of ACE-2/ANG 1-7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis

AimRecent findings have suggested that a therapeutic approach to amplify or stimulate the angiotensin-converting enzyme-2 ACE-2]-angiotensin 1–7 ANG 1–7] mas axis could provide protection against the development of cardiovascular diseases. We investigated the cardioprotective effects of telmisartan in rats with dilated cardiomyopathy DCM] after experimental autoimmune myocarditis EAM].Main methodsDCM was elicited in Lewis rats by immunization with cardiac myosin, and twenty-eight days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg/kg/day) or vehicle.Key findingsTelmisartan treatment effectively suppressed myocardial protein and mRNA expressions of inflammatory markers CD68, iNOS, NF-kB, interleukin-1β, interferon-γ, monocyte chemotactic protein-1] in comparison to vehicle-treated rats. In contrast, myocardial protein levels of ACE-2 and ANG 1–7 mas receptor were upregulated in the telmisartan-treated group compared with vehicle-treated rats. Telmisartan treatment significantly reduced fibrosis and hypertrophy and their marker molecules OPN, CTGF, TGF-β1 and collagens I and III and atrial natriuretic peptide and GATA-4, respectively] compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly lowered the protein expressions of NADPH oxidase subunits p47phox, p67phox, and superoxide production when compared with vehicle-treated rats. Telmisartan treatment significantly decreased the expression levels of mitogen-activated protein kinase (MAPK) signaling molecules than with those of vehicle-treated rats. Also, telmisartan treatment significantly improved LV systolic and diastolic function.SignificanceThese results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling through the modulation of ACE-2/ANG 1–7/Mas receptor axis in rats with DCM after EAM.