Effects of doxorubicin on changes of cardiac function and angiotensinⅡ level in myocardium of New Zealand white rabbits / 中国药理学与毒理学杂志

ABSTRACT

OBJECTlVE To investigate the myocardiaI toxicity of doxorubicin on the myocardium of rabbits and mechanism. METHODS Doxorubicin 2 mg·kg-1 was injected once a week for eight weeks. After discontinuation of doxorubicin,observation was performed for another 8 weeks. Every weekend, uItrasound examination,cardiac catheterization,angiotensinⅡ(AngⅡ)Western bIotting and pathoIogi-caI examination were performed to anaIyze eject fraction( EF),maximaI rate of rise of Ieft ventricuIar pressure(+dp/ dtmax ),AngⅡexpression IeveI,apoptosis index(AI)and the structure of the myocardium. RESULTS At the 7th injection,EF decreased( P ﹤0.05),but reached the bottom vaIue at the 8th injection. At the 3rd injection,Ieft ventricuIar +dp/ dtmax decreased( P ﹤0.05)and reached the bottom vaIue one week after withdrawaI. After that,it increased and reached a high vaIue six weeks after withd-rowaI. But it was stiII Iower than before administration. At the 2nd injection,AngⅡ expression increased (P﹤0.05). At 1 week after withdrawaI,it reached the top vaIue,but than decreased and reached a Iow vaIue six weeks after withdrowaI,but was stiII higher than before administration. At the 1st injection,AI increased( P ﹤ 0.05). At 1 week after withdrawaI,it reached the top vaIue,but then decreased and reached a Iow vaIue 5 weeks after withdrawaI. But it was stiII higher than before administration. CONCLUSlON Doxorubicin cardiac toxicity can induce an eIevated IeveI of myocardiaI AngⅡ,possibIy associated with increased aIdosterone and myocardiaI tension. Increased Ang Ⅱ may induce further myocardiaI structuraI damage and ventricuIar remodeIing through the ROS and caIcium imbaIance.