Upregulation of angiotensin II type 2 receptor and limitation of myocardial stunning by angiotensin II type 1 receptor blockers during reperfused myocardial infarction in the rat.
Upregulation of angiotensin II type 2 receptor and limitation of myocardial stunning by angiotensin II type 1 receptor blockers during reperfused myocardial infarction in the rat.
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DOI：
10.1177/107424840300800307
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
Menon, Vijayan
中科院分区：
文献类型：
--
作者：
Jugdutt, Bodh I.;Menon, Vijayan
背景资料：我们以前已经表明，血管紧张素II 1型受体阻滞剂诱导心脏保护和上调血管紧张素II 2型受体在体内缺血后再灌注犬。血管紧张素II 1型受体阻滞剂是否上调大鼠血管紧张素II 2型受体是有争议的，以及是否可克服和不可克服的血管紧张素II 1型受体阻滞剂在再灌注心肌梗死期间发挥类似的保护作用尚不清楚。研究方法：我们评估了血管紧张素受体拮抗剂缬沙坦和血管紧张素受体拮抗剂厄贝沙坦对血流动力学和左心室收缩和舒张功能的影响（超声心动图/多普勒）体内和梗死面积（氯化三苯基四氮唑法）和局部血管紧张素II 1型受体和血管紧张素II 2型受体表达（免疫印迹）离体，在大鼠的前壁再灌注心肌梗死后。将大鼠随机分为4组：再灌注心肌梗死前30分钟静脉注射缬沙坦（10 mg/kg，n=8）、厄贝沙坦（10 mg/kg，n=8）或生理盐水溶剂（对照组，n=14）和假手术组（n=8）。通过抑制血管紧张素II升压反应来评估血管紧张素II 1型受体阻滞。结果如下：与对照组相比，两种血管紧张素受体阻滞剂均能显著缩小心肌梗死再灌注后的梗死面积，限制左房压的升高，改善左室正dp/dtmax和dP/dtmin，改善左室射血分数和舒张功能，限制梗死范围的扩大。两种血管紧张素受体阻滞剂都增加了缺血后再灌注区的血管紧张素II 2型受体蛋白，而血管紧张素II 1型受体蛋白没有变化。假手术组无变化。结论：总体结果表明，血管紧张素受体阻滞剂缬沙坦和厄贝沙坦都诱导心脏保护，限制心肌顿抑，并上调血管紧张素II 2型受体蛋白表达后再灌注心肌梗死大鼠。已经接受血管紧张素受体阻滞剂并发生急性冠脉综合征的患者可能在再灌注治疗期间受益于这些心脏保护作用。
Background: We have previously shown that angiotensin II type 1 receptor blockers induce cardioprotection and upregulate angiotensin II type 2 receptor during in vivo postischemic-reperfusion in dogs. Whether angiotensin II type 1 receptor blockers upregulate angiotensin II type 2 receptors in rats is controversial, and whether surmountable and insurmountable angiotensin II type 1 receptor blockers exert similar protective effects during reperfused myocardial infarction is not known. Methods: We assessed the effects of the surmountable angiotensin receptor blocker valsartan, and the insurmountable angiotensin receptor blocker irbesartan, on hemodynamics and left ventricular systolic and diastolic function (echocardiography/Doppler) in vivo and infarct size (triphenyl tetrazolium chloride method), and regional angiotensin II type 1 receptor and angiotensin II type 2 receptor expression (immunoblots) ex vivo, after anterior reperfused myocardial infarction in rats. The rats were randomized to four groups: intravenous valsartan (10 mg/kg, n=8), irbesartan (10 mg/kg, n=8), or saline vehicle (controls, n=14) over 30 minutes before reperfused myocardial infarction, and sham (n=8). Angiotensin II type 1 receptor blockade was assessed by the inhibition of angiotensin II pressor responses. Results: Compared with the control group, both angiotensin receptor blockers significantly decreased infarct size, limited the increase in left atrial pressure, improved positive left ventricular dp/dtmax, and dP/dtmin, improved left ventricular ejection fraction and diastolic function, and limited infarct expansion after reperfused myocardial infarction. Both angiotensin receptor blockers increased angiotensin II type 2 receptor protein in the postischemic-reperfused zone, with no change in angiotensin II type 1 receptor protein. There were no changes in the sham group. Conclusion: The overall results indicate that the angiotensin receptor blockers valsartan and irbesartan both induce cardioprotection, limit myocardial stunning, and upregulate angiotensin II type 2 receptor protein expression after reperfused myocardial infarction in the rat. Patients who are already receiving angiotensin receptor blockers and develop acute coronary syndromes might benefit from these cardioprotective effects during reperfusion therapy.