Ryckwaert Frédérique, Colson Pascal, Guillon Gilles, Foëx Pierre
Unité INSERM U469, rue de la Cardonille, Montpellier 34094, France.
Pharmacol Res. 2005 Jun;51(6):497-502. doi: 10.1016/j.phrs.2004.12.003.
Though ischaemia/reperfusion injury induces renin-angiotensin systemic (RAS) activation and increased heart angiotensin production, the effects of blockade of the two main angiotensin II receptors, AT1 and AT2, are not definitively established. Using a Langendorff heart preparation, effects of Valsartan 10(-7)M (AT1 receptor blocker), PD 123319 10(-7)M (AT2 receptor blocker) or both in the presence of a controlled concentration of angiotensin II (10(-8)M) in order to reproduce systemic RAS activation were studied in adult male Wistar rat hearts submitted to ischaemia/reperfusion. Ischaemia/reperfusion impaired both systolic and diastolic function through a no-reflow phenomenon. Presence of a controlled concentration of angiotensin in the perfusate, enough to produce a significant AT1-induced vasoconstriction before ischaemia, has no relevant influence on ischaemia/reperfusion injury. Only blockade of both AT1 and AT2 receptors significantly improved recovery from ischaemia; better ventricle function paralleled better perfusion. The results suggest that blockade of angiotensin II receptors is cumulative since blockade of AT1 and AT2 receptors is more effective than blockade of just one of them.
尽管缺血/再灌注损伤会诱导肾素-血管紧张素系统（RAS）激活并增加心脏血管紧张素的生成，但阻断两种主要的血管紧张素II受体（AT1和AT2）的效果尚未明确确定。使用Langendorff心脏制备方法，在成年雄性Wistar大鼠心脏中进行缺血/再灌注实验，研究了10(-7)M缬沙坦（AT1受体阻滞剂）、10(-7)M PD 123319（AT2受体阻滞剂）或两者在存在可控浓度血管紧张素II（10(-8)M）的情况下的作用，以重现全身RAS激活。缺血/再灌注通过无复流现象损害了收缩和舒张功能。灌注液中存在可控浓度的血管紧张素，足以在缺血前产生显著的AT1诱导的血管收缩，但对缺血/再灌注损伤没有相关影响。只有同时阻断AT1和AT2受体才能显著改善缺血后的恢复；更好的心室功能与更好的灌注平行。结果表明，血管紧张素II受体的阻断具有累积效应，因为同时阻断AT1和AT2受体比仅阻断其中之一更有效。
