Different roles of PPAR-γ activity on physiological and pathological alteration after myocardial ischemia

J Cardiovasc Pharmacol. 2012 Aug;60(2):158-64. doi: 10.1097/FJC.0b013e3182592d7b.

Abstract

Background: Telmisartan is an angiotensin II receptor blocker, which acts as a partial agonist of peroxisome proliferator activator receptor-γ (PPAR-γ). Because PPAR-γ initiates a variety of antiinflammatory responses, the effect on myocardial ischemia is to be elucidated.

Methods and results: The left anterior descending arteries were ligated to induce myocardial infarction in rats. The animals were assigned to 4 groups: (1) control (saline, n = 6), (2) telmisartan (10 mg·kg·d, n = 6), (3) telmisartan + GW9662 (PPAR-γ-antagonist) (10 mg·kg·d of telmisartan and 1 mg·kg·d of GW9662, n = 6), and (4) amlodipine (10 mg·kg·d, n = 8) groups. Telmisartan reduced mean blood pressure compared with that in the control group. There was no statistical difference among the telmisartan, telmisartan + GW9662 and amlodipine groups. The end-diastolic left ventricular diameter was smaller in telmisartan group compared with that in the control group; GW9662 negated the effect of telmisartan. The thickness of the ventricular septum was kept in the telmisartan group compared with that in the control group; GW9662 negated the effect. Histopathologic analyses showed that telmisartan suppressed myocardial fibrosis compared with that of the control, whereas GW9662 negated the telmisartan effect.

Conclusions: Telmisartan suppresses pathological remodeling by PPAR-γ agonistic activities independent of its antihypertensive effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amlodipine / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Anilides / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Benzimidazoles / pharmacology*
  • Benzoates / pharmacology*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Disease Models, Animal
  • Drug Partial Agonism
  • Fibrosis
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Left Ventricular / physiopathology
  • Hypertrophy, Left Ventricular / prevention & control
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • PPAR gamma / agonists*
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / metabolism
  • Pioglitazone
  • Rats
  • Rats, Sprague-Dawley
  • Stroke Volume / drug effects
  • Telmisartan
  • Thiazolidinediones / pharmacology
  • Time Factors
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling / drug effects

Substances

  • 2-chloro-5-nitrobenzanilide
  • Angiotensin II Type 1 Receptor Blockers
  • Anilides
  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Calcium Channel Blockers
  • PPAR gamma
  • Thiazolidinediones
  • Amlodipine
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Telmisartan
  • Pioglitazone