gw9662 and Hypertrophy--Left-Ventricular

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

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Anilides; Animals; Antihypertensive Agents; Benzimidazoles; Benzoates; Blood Pressure; Calcium Channel Blockers; Cells, Cultured; Disease Models, Animal; Drug Partial Agonism; Fibrosis; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Myocardial Infarction; Myocardium; Pioglitazone; PPAR gamma; Rats; Rats, Sprague-Dawley; Stroke Volume; Telmisartan; Thiazolidinediones; Time Factors; Ventricular Function, Left; Ventricular Remodeling