title: Cardioprotective role of peroxisome proliferator-activated receptor-γ agonist, rosiglitazone in a unique murine model of diabetic cardiopathy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  RSZ shows its anti-diabetic effect from 0.3mg/kg dose onwards and at 3mg/kg dose levels it caused beneficial effects (reduction of blood pressure) on cardiovascular system and at highest (30mg/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 2mg/kg the reversal of the adverse effects was evident, indicating the combination of RSZ and amiloride is beneficial in diabetic cardiopathy model.
  
  
  CONCLUSIONS
  RSZ and amiloride combination appeared promising treatment in diabetic patients with cardiopathy without any side effect.
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India; Department of Pharmacology & Toxicology, Bombay Veterinary College, Parel, Mumbai 400012, India. Electronic address: drsureshgiri76@gmail.com.
authors.forename: Suresh R
authors.initials: SR
authors.lastname: Giri
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India.
authors.forename: Bibhuti
authors.initials: B
authors.lastname: Bhoi
authors.affiliation: Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382 213, Gujarat, India.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
authors.affiliation: Department of Pharmacology & Toxicology, Bombay Veterinary College, Parel, Mumbai 400012, India.
authors.forename: Madhumanjiri M
authors.initials: MM
authors.lastname: Gatne
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D048909:Diabetes Complications; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: Amiloride; Diabetic cardiopathy; PPAR gamma agonist; Rosiglitazone; Type 2 diabetes mellitus