Effects and mechanism of fenofibrate and pioglitazone on ventricular remodelingin in pressure overload rats / 中国病理生理杂志

ABSTRACT

AIM:To study the effects and mechanism of peroxisome proliferator-activated receptors(PPARs)ligands,fenofibrate and pioglitazone,on ventricular remodeling in pressure overload rats.METHODS:A pressure overload model was established by the constriction of abdominal aorta in Wistar rats.The hemodynamics and ventricular remodeling parameters,plasma and myocardial renin activity,angiotensin Ⅱ and aldosteron,the mRNA expression of angiotensin Ⅱ type 1 receptor(AT1)were investigated in the constriction of abdominal aorta group(CAA group,n=7)at 12-week after operation and treated experimental groups in which rats were treated with fenofibrate(F group,n=8),pioglitazone(P group,n=7),concomitant fenofibrate and pioglitazone(F+P group,n=6)for 12 weeks since 2 days after operation.The sham-operated rats served as controls(n=8).RESULTS:The ratio of left ventricular weight to body weight,mean arterial pressure,left ventricular systolic pressure,left ventricular end diastolic pressure,left ventricular systolic pressure and heart rate were significantly lower,the maximum left ventricular pressure rising and declining rates(?dp/dtmax)were significantly higher in all treated experimental groups than those in CAA group.Fenofibrate or pioglitazone had no effect on plasma and myocardial levels of renin,angiotensin Ⅱand aldosteron.The mRNA expression of AT1 was downregulated in treated groups except F group.CONCLUSION:PPAR ligands have no effect on plasma and myocardial levels of renin,angiotensin Ⅱand aldosteron,but fenofibrate and pioglitazone inhibit ventricular remodeling,decrease preload and afterload,increase ?dp/dtmax in pressure overload rats.The expression of mRNA of AT1 is downregulated in myocardium of pressure overload rats by the PPAR? signaling pathway.