Yang B C, Phillips M I, Ambuehl P E, Shen L P, Mehta P, Mehta J L
Department of Medicine, University of Florida and VA Medical Center, Gainesville 32610, USA.
Circulation. 1997 Aug 5;96(3):922-6. doi: 10.1161/01.cir.96.3.922.
Myocardial ischemia is known to upregulate the systemic renin-angiotensin system, which influences myocardial ischemic events by affecting hemodynamics and hemostatic activity. This study was designed to examine whether angiotensin II (Ang II) receptor expression in the myocardium is altered immediately after ischemia-reperfusion.
Isolated buffer-perfused Sprague-Dawley rat hearts were subjected to continuous perfusion (control, n=5) or to 25 minutes of global ischemia followed by 30 minutes of reperfusion (n=10). Autoradiographic analysis for Ang II receptors of multiple myocardial sections was performed. Whereas continuous perfusion of hearts resulted in minor changes in coronary perfusion pressure (CPP), left ventricular end-diastolic pressure (LVEDP), and developed left ventricular pressure (dLVP=LVSP-LVEDP), ischemia-reperfusion caused a marked increase in CPP and LVEDP and a decrease in dLVP, indicating severe cardiac dysfunction. Concurrently, total myocardial Ang II receptor expression was greater (P<.05) in hearts subjected to ischemia-reperfusion than in the continuously perfused control hearts. Most of the increase in Ang II receptor expression was due to an increase in type 1 receptor (AT1) expression (34.6+/-6.5 versus 18.2+/-4.4 fmol/g, P<.05), because Ang II type 2 receptor expression was unaffected. To examine the importance of AT1 receptor expression, another group of isolated rat hearts (n=5) was perfused with buffer containing losartan (10(-5) mol/L) and subjected to ischemia followed by reperfusion. Perfusion of hearts with losartan attenuated the ischemia-reperfusion-induced cardiac dysfunction. Perfusion of hearts with losartan also blocked the ischemia-reperfusion-induced increase in myocardial AT1 binding.
These observations indicate that myocardial AT1 expression increases immediately after ischemia-reperfusion and contributes to cardiac dysfunction.
已知心肌缺血会上调全身肾素 - 血管紧张素系统，该系统通过影响血流动力学和止血活性来影响心肌缺血事件。本研究旨在检查心肌缺血再灌注后心肌中血管紧张素 II（Ang II）受体表达是否立即发生改变。
将离体缓冲液灌注的斯普拉格 - 道利大鼠心脏进行持续灌注（对照组，n = 5）或进行25分钟全心缺血，随后再灌注30分钟（n = 10）。对多个心肌切片进行Ang II受体的放射自显影分析。持续灌注心脏导致冠状动脉灌注压（CPP）、左心室舒张末期压力（LVEDP）和左心室发展压力（dLVP = LVSP - LVEDP）有轻微变化，而缺血再灌注导致CPP和LVEDP显著升高，dLVP降低，表明严重的心功能障碍。同时，缺血再灌注心脏的总心肌Ang II受体表达比持续灌注的对照心脏更高（P <.05）。Ang II受体表达的增加主要是由于1型受体（AT1）表达增加（34.6±6.5对18.2±4.4 fmol/g，P <.05），因为2型Ang II受体表达未受影响。为了检查AT1受体表达的重要性，另一组离体大鼠心脏（n = 5）用含氯沙坦（10⁻⁵ mol/L）的缓冲液灌注，然后进行缺血再灌注。用氯沙坦灌注心脏可减轻缺血再灌注诱导的心功能障碍。用氯沙坦灌注心脏也可阻断缺血再灌注诱导的心肌AT1结合增加。
这些观察结果表明，心肌缺血再灌注后心肌AT1表达立即增加，并导致心功能障碍。
