Damage To The Heart Induced By Excess Alcohol Consumption And The Protective Effect Of ACEI In Rat

Objective This study was designed to determine the effect of excess alcohol consumption on cardiac structure and function. We also investigated whether angiotensin converting enzyme inhibitors(ACEI) could provide protection from alcoholic heart damage. Methods 40 rats were randomly divided into four groups: control(C) group, alcohol(A) group, low-dose ACEI(P1) group and high-dose ACEI(P2) group,10 for each group. They were arranged for intragastric administration of alcohol, and given ACEI as a protector. After 10 weeks, Echocardiography and Ultrastructural exam were performed on the rats to assess the cardiac structure and function. Body mass (BM) and relative heart mass were measured, then expressions of mRNA of biochemical molecules in myocardium, such as ACE, angiotensinogen(AGT), TNF-α, endothelin-1 (ET-1), angiotensin receptor 1 (AT1) and angiotensin receptor 2 (AT2) were measured by reverse transcriptase polymerase chain reaction (RT-PCR), the content of hydroxyproline(Hyp) was measured by Sample Alkaline Solution method. Results (1) The BM of A, P1 and P2 groups decreased after 10 weeks compared with C group(P<0.05), and there is no significant differences among these three groups(P>0.05). The relative heart mass of A group increased compared with the other groups(P<0.05), and the value of P1 group was higher than P2 group(P<0.05). (2) The LVEDd,LVEDs of A group were larger compared with the other three groups(P<0.05), and IVSd,IVSs,LVPDd,LVPDs showed no difference among the four groups(P>0.05). Among the four groups, there was no difference on the systolic LV function parameters(P>0.05), such as ejection fraction(EF), fractional shortening(FS) and stroke volume(SV). The diastolic function indices, such as E,Ea and Ea/Aa of A group decreased compared with the other groups(P<0.05), and Aa of A group increased compared with other groups(P<0.05). (3) It was showed on ultrastructure that cardiac cells in A group presented mitochondrial swelling, hydropic change, and most of the cristae disappearing, while cells in the C, P1 and P2 groups with less damage in mitochondria. (4) The mRNA expressions of ACE and TNF-αof A group increased compared the other three groups(P<0.05). The mRNA expression of AGT of A group increased compared with C and P2 groups(P<0.05), and this value of P1 group increased compared with P2 group(P<0.05). The mRNA expressions of ET-1 of A, P1 and P2 groups increased compared with C group(P<0.05), and the value of P2 group decresed compared with A and P1 groups(P<0.05). The mRNA expressions of AT1 and AT2 showd no difference among the four groups (P>0.05). (5) The content of hydroxyproline in myocardium of A group was more than C and P2 groups(P<0.05), and this value of P1 group was more than C group. (6) By Pearson correlation analysis, ACE was positively related with AGT, ET-1 and Hyp, respectively(r=0.440, P=0.010;r=0.595, P=0.000; r=0.418, P=0.016); and Hyp was positively related with ET-1 (r=0.616, P=0.000). Conclusion Local rennin-angiotensin system in myocardium was activated after excess alcohol consumption, with the mRNA expression of ACE, AGT, TNF-α, ET-1, and the content of hydroxyproline increasing, so that it induced ultrastructure changes and diastolic dysfunction of heart. The present study concluded that ACEI could protect the cardiac myocyte from the injury of over alcohol consumption.