The effect of PPAR-γ agonist (rosiglitazone) and angiotensin II receptor blocker (losartan) on the myocardial structure and function assessed with two-dimensional echocardiography and strain rate ima

Abstract

[영문]

Myocardial dysfunction is more frequently observed in diabetic patients with albuminuria. The aim of this study was to investigate the effect of the peroxisome proliferator-activated receptor (PPAR) ligands and the angiotensin II receptor blocker (ARB) on myocardial structure and function and the association with the degree of albuminuria in the type 2 diabetic rat model. Five male Long-Evans Tokushima Otsuka (LETO) rats and 20 male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used. The animals were divided into five groups at 28 weeks of age as follows: untreated LETO rats, untreated OLETF rats, OLETF rats treated with losartan, OLETF rats treated with rosiglitazone and OLETF rats treated with a combination of both drugs. The ARB, losartan was given in the dose of 5 mg/kg/d and the PPAR-gamma agonist, rosiglitazone was given in the dose of 3 mg/kg/d, by oral gavage for a subsequent 12 weeks. At 28 weeks and at 40 weeks, urine samples and blood samples were collected and two-dimensional echocardiogram and strain rate imaging were obtained for the assessment of myocardial structure and function. At the end of the experimental period, hearts were rapidly excised for histological analysis.The OLETF rats showed increased fasting glucose levels, fasting insulin levels and urine albumin/creatinine ratio compared with the LETO rats not only at 28 weeks but also at 40 weeks. At 40 weeks, it showed better metabolic profiles in the rosiglitazone group and in the combination group than in the untreated or the losartan group. The losartan-treated or combination drug-treated OLETF rats showed a significant attenuation in the progression of albuminuria. The expression of growth factors (TGF-β and TNF-α) and proinflammatory cytokines (IL-1 and IL-6) in cardiac tissue increased significantly in the OLETF rats compared with the LETO rats. After treatment with losartan or combination with losartan plus rosiglitazone, the expression those growth factors and cytokines in the OLETF cardiac tissue attenuated. In the cardiac structure and functional analysis, the histological results including a degree of interstitial fibrosis and collagen interposition of left ventricle revealed that interstitial fibrosis was also attenuated in the losartan group and the combination group than the untreated OLETF group. I could see consistent results in the comparison of collagen type I and III expression in left ventricle and the echocardiographic parameters assessed with two-dimensional echocardiography and strain rate imaging. In conclusion, the ARB, losartan revealed protective effect on the progression of albuminuria, myocardial structural and functional changes. The PPAR-r agonist, rosiglitazone showed minimal protective effect on the progression of albuminuria and no significant myocardial structural and functional benefits even though it had a metabolic benefits. The combination of losartan and rosiglitazone showed both metabolic benefits and myocardial protective effects.