Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, University Campus, Zografou, Athens 15771, Greece.
Cardiol Res Pract. 2012;2012:986813. doi: 10.1155/2012/986813. Epub 2012 Jul 12.
Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts. Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n = 39) and ETB-deficient (n = 41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion. Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P = 0.006) in wild-type (31.5 ± 4.4%) than ETB-deficient (45.0 ± 7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion. Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases.
内皮素-1(ET-1)参与缺血再灌注后的左心室功能障碍。ETA 和 ETB 受体介导多种作用,但尚不清楚这些作用是否取决于缺血类型和持续时间。我们研究了 ETB 受体在四种缺血再灌注方案后在分离的大鼠心脏中的作用。
在 Langendorff 灌注模型中,测量 40 分钟和 20 分钟区域性或全区域性缺血后,再灌注 30 分钟后的左心室血流动力学变量。比较野生型(n = 39)和 ETB 缺陷型(n = 41)大鼠。使用荧光微球测量区域性缺血再灌注后的梗塞面积。
左心室功能障碍在 ETB 缺陷型大鼠中更为明显,尤其是在区域性缺血后。在野生型(31.5 ± 4.4%)大鼠中,梗塞面积小于 ETB 缺陷型(45.0 ± 7.3%)大鼠(P = 0.006)。尽管 40 分钟缺血再灌注后左心室功能的恢复较差,但 ETB 缺陷型大鼠的舒张末期压在 20 分钟比 40 分钟区域性缺血再灌注后更高。
ETB 受体在大鼠心脏中发挥细胞保护作用,主要在区域性缺血再灌注后。较长时间的缺血会抑制再灌注后左心室功能的恢复,但 ETB 受体的作用在早期阶段可能更为重要。