title: Different roles of PPAR-γ activity on physiological and pathological alteration after myocardial ischemia.
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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nagashima
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Masumura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hishikari
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takayama
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D054333:Drug Partial Agonism; D005355:Fibrosis; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D047228:Angiotensin II Type 1 Receptor Blockers; D000813:Anilides; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D047495:PPAR gamma; D045162:Thiazolidinediones; D017311:Amlodipine; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D000077333:Telmisartan; D000077205:Pioglitazone