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

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Life sciences (Impact Factor: 2.7). 12/2011; 90(7-8):289-300. DOI: 10.1016/j.lfs.2011.11.018
Source: PubMed


Recent 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].
DCM 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 (10mg/kg/day) or vehicle.
Telmisartan 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.
These 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.

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    • "In a model of ADR-induced heart failure in Male Sprague-Dawley rats, Zong et al (2011) detected a decrease of plasma Ang-(1–7) levels and reduced myocardial expression of Mas receptor, while the treatment with telmisartan or losartan increased Ang-(1–7) levels and suppressed myocardial AT1 receptor expression without changing the expression of Mas [58]. Recent studies of Sukumaran et al (2011 and 2012) showed that the protein and mRNA levels of Mas receptor, ACE2 and Ang-(1–7) were upregulated in olmesartan treated group in experimental autoimmune myocarditis and these changes in RAS components decreased the expression of inflammatory markers [56], [57]. Taken together, these findings indicated that ACE2/Ang-(1–7)/Mas receptor axis activation participate in the renoprotection triggered by ARB "
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