title: Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in Zucker diabetic fatty rats with metabolic syndrome.
abstract: OBJECTIVE
  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-κB, 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 associated with increased adiponectin and a decrease in inflammatory markers.
authors: Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Second University of Naples, Via Costantinopoli 16, Naples, Italy.
authors: B
authors: B
authors: Rinaldi
authors: C
authors: C
authors: Di Filippo
authors: A
authors: A
authors: Capuano
authors: M
authors: M
authors: Donniacuo
authors: L
authors: L
authors: Sodano
authors: F
authors: F
authors: Ferraraccio
authors: F
authors: F
authors: Rossi
authors: M
authors: M
authors: D'Amico
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007150:Immunohistochemistry; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000097:blood / Q000187:drug effects*; D051381:Rats; D011924:Rats, Zucker; D000077333:Telmisartan; D019210:Troponin I / Q000097:blood / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D002316:Cardiotonic Agents; D016328:NF-kappa B; D047495:PPAR gamma; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D000077333:Telmisartan