Article

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: 2.56). 12/2011; 90(7-8):289-300. DOI:10.1016/j.lfs.2011.11.018 pp.289-300
Source: PubMed

ABSTRACT 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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Keywords

ACE-2/ANG 1-7/Mas receptor axis
 
ANG 1-7 mas receptor
 
angiotensin-converting enzyme-2 [ACE-2]-angiotensin 1-7 [ANG 1-7] mas axis
 
atrial natriuretic peptide
 
cardiac myosin
 
cardiovascular diseases
 
diastolic function
 
dilated cardiomyopathy [DCM]
 
experimental autoimmune myocarditis [EAM]
 
inflammatory markers [CD68
 
LV function
 
marker molecules [OPN
 
mitogen-activated protein kinase
 
monocyte chemotactic protein-1]
 
myocardial protein levels
 
surviving Lewis rats
 
telmisartan
 
Telmisartan treatment
 
telmisartan-treated group
 
therapeutic approach