Pioglitazone ameliorates systolic and diastolic cardiac dysfunction in rat model of angiotensin II-induced hypertension

作者：Sakamoto Aiko; Hongo Makiko; Furuta Kyoko; Saito Kan; Nagai Ryozo; Ishizaka Nobukazu^*

来源：International Journal of Cardiology, 2013, 167(2): 409-415.

DOI：10.1016/j.ijcard.2012.01.007

• Angiotensin II
• Lipid accumulation
• Peroxisome proliferator activated receptor
• Cardiac function

We previously showed that administration of angiotensin II to rats causes fibrosis and lipid accumulation in the heart. In the current study, we examined the effect of pioglitazone, an agonist of peroxisome proliferator activated receptor-gamma, on angiotensin II-induced intracardiac lipid accumulation and cardiac dysfunction. Pioglitazone, given orally at a dose of 2.5 mg/kg/d, reduced cardiac triglyceride content and suppressed lipid deposition in the heart of angiotensin II-induced hypertensive rats without affecting angiotensin II-induced upregulation of lipogenic gene expression. Histological examination showed that pioglitazone reduced the area of cardiac fibrosis and iron deposition in the heart of angiotensin II-treated rats. Expression of an antioxidative molecule, heme oxygenase-1, was increased by angiotensin II infusion, and pioglitazone treatment preserved expression of HO-1. Angiotensin II increased the superoxide signals detected by dihydroethidium staining in myocardial cells with lipid deposition, and this increase was suppressed by pioglitazone. Cardiac function was analyzed in an ex vivo isolated cardiac perfusion system. It was found that pioglitazone improved both the systolic and diastolic cardiac performance, which was weakened by angiotensin II infusion, after transient ischemia and reperfusion. These findings collectively suggest that pioglitazone treatment ameliorated the histological and functional cardiac damage induced by angiotensin II infusion, the mechanism of which may be related to the antioxidative action of pioglitazone.

• 出版日期2013-7-31