Different Roles of PPAR-gamma Activity on Physiological and Pathological Alteration After Myocardial Ischemia

作者:Nagashima Ayako; Watanabe Ryo; Ogawa Masahito; Suzuki Jun ichi*; Masumura Mayumi; Hishikari Keiichi; Shimizu Tomoko; Takayama Kiyoshi; Hirata Yasunobu; Nagai Ryozo; Isobe Mitsuaki
来源:Journal of Cardiovascular Pharmacology, 2012, 60(2): 158-164.
DOI:10.1097/FJC.0b013e3182592d7b

摘要

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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusions: Telmisartan suppresses pathological remodeling by PPAR-gamma agonistic activities independent of its antihypertensive effects.

  • 出版日期2012-8