Cardioprotective role of peroxisome proliferator-activated receptor-γ agonist, rosiglitazone in a unique murine model of diabetic cardiopathy

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Aims:Rosiglitazone (RSZ), a PPARγ agonist was potent efficacious insulin sensitizing blockbuster drug for treatment of Type 2 diabetes mellitus (T2DM) but the benefit of PPARγ activation in congestive heart failure (CHF) was controversial. The present work was planned to study the role of RSZ in diabetic cardiopathy.Main methods:Zucker fa/fa rats, the genetic model of T2DM were subjected to constriction of suprarenal abdominal aorta so that they represent a combined model of diabetes and cardiopathy. The development cardiopathy was assessed biochemically (plasma BNP and aldosterone levels), using echocardiography and expression angiotensin II receptor type 1a gene in heart and Endothelin-1 gene in aorta. Rats were treated with RSZ and in combination with amiloride for four weeks and were assessed to evaluate the effect of RSZ or amiloride or its combination on antidiabetic activity, adverse or toxic effects and congestive heart failure status.Key findings:RSZ shows its anti-diabetic effect from 0.3 mg/kg dose onwards and at 3 mg/kg dose levels it caused beneficial effects (reduction of blood pressure) on cardiovascular system and at highest (30 mg/kg) dose it starts showing adverse effects like body weight gain, edema, left ventricular hypertrophy. However, when highest dose of RSZ animals were treated with amiloride (ENaC inhibitor) at 2 mg/kg the reversal of the adverse effects was evident, indicating the combination of RSZ and amiloride is beneficial in diabetic cardiopathy model.Significance:RSZ and amiloride combination appeared promising treatment in diabetic patients with cardiopathy without any side effect.

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