Xu Yi, Kumar Dinender, Dyck Jason R B, Ford William R, Clanachan Alexander S, Lopaschuk Gary D, Jugdutt Bodh I
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2R7.
Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1206-15. doi: 10.1152/ajpheart.00839.2000.
We assessed ANG II type 1 (AT(1)) and type 2 (AT(2)) receptor (R) expression and functional recovery after ischemia-reperfusion with or without AT(1)R/AT(2)R blockade in isolated working rat hearts. Groups of six hearts were subjected to global ischemia (30 min) followed by reperfusion (30 min) and exposed to no drug and no ischemia-reperfusion (control), ischemia-reperfusion and no drug, and ischemia-reperfusion with losartan (an AT(1)R antagonist; 1 micromol/l), PD-123319 (an AT(2)R antagonist; 0.3 micromol/l), N(6)-cyclohexyladenosine (CHA, a cardioprotective adenosine A(1) receptor agonist; 0.5 micromol/l as positive control), enalaprilat (an ANG-converting enzyme inhibitor; 1 micromol/l), PD-123319 + losartan, ANG II (1 nmol/l), or ANG II + losartan. Compared with controls, ischemia-reperfusion decreased AT(2)R protein (Western immunoblots) and mRNA (Northern immunoblots, RT-PCR) and impaired functional recovery. PD-123319 increased AT(2)R protein and mRNA and improved functional recovery. Losartan increased AT(1)R mRNA (but not AT(1)R/AT(2)R protein) and impaired recovery. Other groups (except CHA) did not improve recovery. The results suggest that, in isolated working hearts, AT(2)R plays a significant role in ischemia-reperfusion and AT(2)R blockade induces increased AT(2)R protein and cardioprotection.
我们评估了在离体工作大鼠心脏中，缺血再灌注后1型血管紧张素II（AT(1)）和2型（AT(2)）受体（R）的表达及功能恢复情况，以及有无AT(1)R/AT(2)R阻断时的情况。将六组心脏进行全心缺血（30分钟），随后再灌注（30分钟），并分别给予无药物且无缺血再灌注（对照组）、缺血再灌注且无药物、缺血再灌注加氯沙坦（一种AT(1)R拮抗剂；1微摩尔/升）、PD - 123319（一种AT(2)R拮抗剂；0.3微摩尔/升）、N(6)-环己基腺苷（CHA，一种具有心脏保护作用的腺苷A(1)受体激动剂；0.5微摩尔/升作为阳性对照）、依那普利拉（一种血管紧张素转换酶抑制剂；1微摩尔/升）、PD - 123319 + 氯沙坦、血管紧张素II（1纳摩尔/升）或血管紧张素II + 氯沙坦处理。与对照组相比，缺血再灌注降低了AT(2)R蛋白（蛋白质免疫印迹法）和mRNA（Northern免疫印迹法、逆转录聚合酶链反应）水平，并损害了功能恢复。PD - 123319增加了AT(2)R蛋白和mRNA水平，并改善了功能恢复。氯沙坦增加了AT(1)R mRNA（但未增加AT(1)R/AT(2)R蛋白）水平，并损害了恢复。其他组（除CHA外）均未改善恢复情况。结果表明，在离体工作心脏中，AT(2)R在缺血再灌注中起重要作用，阻断AT(2)R可诱导AT(2)R蛋白增加并具有心脏保护作用。
