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

Background: Telmisartan is an angiotensin II receptor blocker, which acts as a partial agonist of peroxisome proliferator activator receptor-gamma (PPAR-gamma). Because PPAR-gamma 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(-1).d(-1), n = 6), (3) telmisartan + GW9662 (PPAR-gamma-antagonist) (10 mg.kg(-1).d(-1) of telmisartan and 1 mg.kg(-1).d(-1) of GW9662, n = 6), and (4) amlodipine (10 mg.kg(-1).d(-1), 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-gamma agonistic activities independent of its antihypertensive effects.