Angiotensin Receptor Expression And Cardiovascular Remodeling In I-R Rat Underarb Pretreatment

Backgroud and object: It is established that AT2 is reexpression in myocardium injury. Study on the long-term effect of ARBs have showed that there was not just a limited to the antagonist of the AT1, the agonist of the AT2 has also became the focus. but there was controversial on the localization, expression, mechanical of signal transduction of AT2 and so on. It has been reported in the model of myocardial infarction and pressure overload rats, myocyte remodeling, Interstitial remodeling and vascular remodeling, but the attention payed on the the long effect of antagionist of RAS in I-R(Ischemia reperfusion ) was little, which is happened frequently in clinical practice. This study focused on the long effect on the distribution, expression, regulation of AT2 in I-R rat under the antagonist pretreatment of RAS.Methods: 148 rats were divided randomly into four groups: Sham group, Control group, ACEI group and ARBs group. The Control group received placebo and ACEI group received fosinpril (5mg/Kg·d) and the ARBs group received valsartan (10mg/Kg·d) respectively via gavage for 4 weeks before surgery. To make I-R model, thorax was opened, and the LAD(left anterior descending coronary artery) was ligated. After 30 minutes' the ligature was removed and the treatment were continued to use till the heart was removed. On the 3th, 7th, 14th, 28th postoperation day, rats were killed for the heart after hemodynamics. The section was stained by picrosirus red and in order to observe collagen deposition in institution and areas around vessels,Immunohistochemical study have been done in order to determine dynamic expression of AT.Results: Institution collagen deposition in the Control group increased grandually, there was significantly difference between the Sham group and the Control group at day 7, 14, 28. However, institution collagen deposition of ACEI group and ARBs group was significantly decreased in compare with Control group. The distribution of AT1 is disperse, the expression was incresed for a short period of time and decreased slowly after I-R. While the distribution of AT2 was localized on the membrane of fibroblast in subendocardial, outer layer of coronary arteries, especially in large coronary arteries. The expression of AT2 was transient after I-R under pretreatment of ACEI and ARB: Its reexpression reached a peak at day 7 in Control grouop, while in ARBs group the peak was earlier and higher than that in the Control group.Conclusions: There occurred Interstitial remodeling after I-R and pretreatment of ACEI and ARB; ACEI, ARBs may inhibit cardiovascular remodeling effectively；the reexpression of AT2 was transient after I-R; It was partly because of the long-term blockade of AT1 after pretreatment of ARBs.