Protective effects of pioglitazone on endothelial function in rats with hypercholesterolemia

AIM: To investigate the effects of pioglitazone,a PPARγ agonist,on endothelial cell (EC) dysfunction in hypercholesterolemic rats.METHODS: 36 healthy male Wistar rats were assigned to one of the following groups randomly (six rats in each group): control,hypercholesterolemia (HC),and HC treated with pioglitazone 1.5 mg·kg^-1·d^-1,3 mg·kg^-1·d^-1,10 mg·kg^-1·d^-1 and 20 mg·kg^-1·d^-1 (HC＋PIO),respectively.EC function was determined by comparing vasorelaxation to ACh,an EC dependent vasodilator,and acidified NaNO₂,an EC-independent vasodilator.Maximal positive and negative values of the instantaneous first derivative of LVP (+dp/dt_max and dp/dt_max) were determined by MS2000 system.RESULTS: (1) Hypercholesterolemia caused a significant endothelial diastolic dysfunction (maximal relaxation to ACh: 50.51%±2.45% vs 99.78%±3.01% in control,P<0.01).(2) Treatment with pioglitazone relieved EC-dependent vasodilatation in a dose dependent manner,and 10 mg·kg^-1·d^-1 is the best dose.(3) Pioglitazone not only improved EC function,but also reduced cardiac functional injury induced by hypercholesterolemia.CONCLUSION: EC dysfunction induced by hypercholesterolemia can be directly extenuated by pioglitazone,which may effectively prevent from subsequent atherosclerosis and ischemic heart disease.