Sun Y, Weber K T
Division of Cardiology, University of Missouri-Columbia 65212.
Cardiovasc Res. 1994 Nov;28(11):1623-8. doi: 10.1093/cvr/28.11.1623.
The aim was to determine angiotensin II receptor binding and its relationship to angiotensin converting enzyme (ACE) binding and fibrous tissue formation in the rat heart.
A model of tissue repair (pericardiotomy and myocardial infarction with left coronary artery ligation) was used together with the following: quantitative in vitro autoradiography to determine angiotensin II receptor (125I[Sar1, Ile8]AngII) and ACE (125I-351A) binding densities. Angiotensin II receptor subtype was determined using an AT1 receptor antagonist (DuP753, losartan) and an AT2 receptor antagonist (PD123177). Five groups were studied: age and sex matched controls receiving this operative procedure without subsequent myocardial infarction (sham operated); rats with coronary artery ligation and myocardial infarction; rats with coronary artery ligation and lisinopril (20 mg.kg-1.d-1 in drinking water); sham operated rats receiving lisinopril; and unoperated rats which served as controls to pericardiotomy. Hearts were collected from each group on postoperative day 3 and weeks 1, 2, 4, and 8.
There was (1) low angiotensin receptor binding in normal myocardium; (2) markedly increased angiotensin II receptor binding at the site of left ventricular myocardial infarction and endocardial fibrosis of the interventricular septum at day 3 and weeks 1, 2, 4, and 8; (3) high angiotensin II receptor binding in the pericardial fibrosis that followed pericardiotomy, and in the fibrosis that appeared in response to suture insertion around the left coronary artery, in both infarcted and sham operated rats; (4) total displacement of normal and connective tissue angiotensin II receptor binding by DuP753, but not by PD123177; (5) ACE inhibition by lisinopril, but no change in angiotensin II receptor binding, at all sites of fibrosis; and (6) significant attenuation by lisinopril of collagen formation in the visceral pericardium of sham operated controls.
In this model of tissue repair, increased AT1 receptor binding density is associated with ACE binding and fibrillar collagen formation that appears within sites of fibrous tissue formation, including myocardial infarction, endocardial fibrosis, foreign body (silk suture), and pericardiotomy. AT1 receptors may play a role in mediating the fibrogenic response to tissue injury in the rat heart.
本研究旨在确定大鼠心脏中血管紧张素 II 受体结合情况及其与血管紧张素转换酶（ACE）结合和纤维组织形成的关系。
采用组织修复模型（心包切开术及左冠状动脉结扎所致心肌梗死），并结合以下方法：定量体外放射自显影法测定血管紧张素 II 受体（125I[Sar1，Ile8]AngII）和 ACE（125I - 351A）的结合密度。使用 AT1 受体拮抗剂（DuP753，氯沙坦）和 AT2 受体拮抗剂（PD123177）确定血管紧张素 II 受体亚型。研究分为五组：年龄和性别匹配的对照组，接受该手术操作但无后续心肌梗死（假手术）；冠状动脉结扎及心肌梗死大鼠；冠状动脉结扎及服用赖诺普利（饮用水中 20 mg·kg-1·d-1）的大鼠；接受赖诺普利的假手术大鼠；以及作为心包切开术对照的未手术大鼠。术后第 3 天以及第 1、2、4 和 8 周从每组收集心脏。
（1）正常心肌中血管紧张素受体结合较低；（2）在术后第 3 天以及第 1、2、4 和 8 周，左心室心肌梗死部位及室间隔心内膜纤维化处血管紧张素 II 受体结合显著增加；（3）心包切开术后的心包纤维化以及梗死和假手术大鼠中因围绕左冠状动脉插入缝线而出现的纤维化中，血管紧张素 II 受体结合较高；（4）DuP753 可完全取代正常组织和结缔组织中的血管紧张素 II 受体结合，但 PD123177 不能；（5）在所有纤维化部位，赖诺普利可抑制 ACE，但血管紧张素 II 受体结合无变化；（6）赖诺普利可显著减轻假手术对照组脏层心包中的胶原形成。
在该组织修复模型中，AT1 受体结合密度增加与 ACE 结合以及纤维组织形成部位（包括心肌梗死、心内膜纤维化、异物（丝线缝合）和心包切开术）出现的纤维状胶原形成相关。AT1 受体可能在介导大鼠心脏对组织损伤的纤维化反应中起作用。
