Premium
Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in zucker diabetic fatty rats with metabolic syndrome
Author(s) -
Rinaldi B.,
Di Filippo C.,
Capuano A.,
Donniacuo M.,
Sodano L.,
Ferraraccio F.,
Rossi F.,
D'Amico M.
Publication year - 2012
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01527.x
Subject(s) - telmisartan , medicine , endocrinology , adiponectin , angiotensin ii receptor type 1 , angiotensin ii , agonist , receptor , diabetes mellitus , insulin resistance , blood pressure
Aim: This study investigated whether telmisartan, a selective angiotensin type 1 (AT1) receptor antagonist and gamma peroxisome proliferator‐activated receptor (PPAR‐ γ ) partial agonist, reduces myocardial ischaemia/reperfusion (I/R) injury in an experimental model of metabolic syndrome. Methods: Zucker Diabetic Fatty (ZDF) rats were treated for 3 weeks with telmisartan at doses of 2, 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25‐min occlusion of the left descending coronary artery followed by 2‐h reperfusion (I/R). Results: Telmisartan reduced the extension of the infarct size in a dose‐dependent fashion and decreased the levels of plasma troponin I, a specific marker of myocardial damage. Telmisartan also caused a dose‐dependent increase in adiponectin both in plasma and cardiac tissue of infarcted ZDF rats. These levels were minimally increased (p < 0.05 vs. vehicle) by telmisartan 7 mg/kg/day and reached the maximum values with the highest dose of 12 mg/kg/day (p < 0.01 vs. vehicle). In contrast, within the infarcted tissue telmisartan decreased the expression of markers of inflammation such as the transcription factor NF‐ κ B, the toll‐like receptors TLR2 and TLR4 as well as TNF‐ α cytokine. Nitrosative stress was maximal in vehicle‐treated infarcted hearts as evidenced by increased expression of iNOS, which was almost abolished after treatement with telmisartan. Conclusions: Treatment of ZDF rats for 3 weeks with telmisartan, a dual angiotensin II receptor antagonist and partial PPAR‐ γ receptor agonist, resulted in a significant reduction of myocardial damage induced by I/R and was assocciated with increased adiponectin and a decrease in inflammatory markers.