Effects Of Pioglitazone And Atorvastatin On Myocardial Hypertrophy Induced By Pressure Overload In Rats

Cardiac hypertrophy is observed in various cardiovascular diseases such as hypertension, valvular heart disease. Clinical studies have demonstrated that cardiac hypertrophy is not only an adaptational state before heart failure but also an independent risk factor for ischemia, arrhythmia and sudden death. So it is important to prevent the development of cardiac hypertrophy.Recent studies have shown that proinflammatory cytokines including interleukin- 1 (IL- ), cardiotropin-1 (CT-1) are expressed within the hypertrophic myocardium induced by pressure overload. Vitro studies have shown that proinflammatory cytokines can induce myocardium hypertrophy and increase the secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) , the markers of cardiac hypertrophy. So the proinflammatory cytokines play some important roles in the pathogenesis of cardiac hypertrophy.The first part of the study was to investigate the effects of pioglitazone on cardiac hypertrophy due to pressure overload, and to evaluate the anti-inflammatory activities of the drug. Cardiac hypertrophy was produced by abdominal aortic banding (AB). Pioglitazone (20mg kg-1 day-1) was given orally 1 week before operation and continued till 4 weeks after operation. After the rats were killed, the pathobiological change of the hearts was measured. The myocardium cytokines (IL- , CT- 1 ) mRNA expression were tested by RT-PCR and immunohistochemistry.The result showed that the mRNA and protein expression of the cytokines IL- 3 and CT-1 were markedly enhanced in the hypertrophic myocardium of AB rats. Treatment of AB rats with pioglitazone significantly inhibited the upregulation ofcytokines mRNA and protein expression and reduced pressure overload-induced increases in heart-to -body weight radio, the left ventricular wall thinkness and myocyte diameter. Suppression of cardiac hypertrophy by pioglitazone was accompanied by a decreased expression of BNP, the molecular marker for cardiac hypertrophy.The aim of the second part of the study was to investigate the antihypertrophic effects of atorvastatin and its effects on proinflammatory cytokines.Cardiac hypertrophy was produced as Part I did. One group of rats were given atorvastatin (5mgkg-1 day"1) orally 1 week before the operation and continued 4 week after the operation. At the same time another group were given atorvastatin( 5mg kg-1day"!) and pioglitazone(20mg kg"1 day"1) together. The other part of the study was done as the part I did.The result showed that treatment of AB rats with atorvastatin siginificantly reduced myocardial cytokines IL-1 3 , CT-1 mRNA and protein expression and inhibited the increases in the heart-to -body weight radio, the left ventricular wall thinkness and myocyte diameter. The expression of BNP was also reduced. The effect of using atorvastatin and pioglitazone together had no statistic difference compared with that using either of the drug only.Conclusion: Both pioglitazone and atorvastatin may regulate cardiac hypertrophy through inhibit the expression of proinflammatory cytokines . The effect of using atorvastatin and pioglitazone together had no statistical difference compared with that when either of the drag used alone.