Lefer A M, Murohara T, Buerke M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Methods Find Exp Clin Pharmacol. 1994 Nov;16(9):623-31.
We examined the effects of taprostene (2.5 x 10(-8) M to 1 x 10(-7) M), a stable prostacyclin analog, on PMN-endothelial interaction (i.e., adherence) and subsequent vasocontraction and endothelial dysfunction. Taprostene effectively inhibited the adherence of leukotriene B4-stimulated autologous cat polymorphonuclear (PMN) leukocytes to isolated cat coronary artery endothelium. Taprostene also inhibited coronary artery vasocontraction to leukotriene B4-stimulated PMNs (p < 0.01). In isolated coronary artery rings stimulated with either 2 U/ml of thrombin or 100 microM hydrogen peroxide (H2O2), adherence of unstimulated PMNs to coronary endothelium was significantly increased, resulting in vasocontraction and subsequent endothelial dysfunction. However, taprostene (1 x 10(-7) M) significantly attenuated unstimulated PMN adherence to stimulated coronary endothelium. This antiadherence action effectively attenuated PMN-induced coronary artery vasocontraction (p < 0.01) and significantly blunted the subsequent PMN-induced endothelial dysfunction (p < 0.01) characterized by a loss of endothelium-derived nitric oxide (NO). Thus, taprostene exerts a profound inhibitory effect on PMN-endothelium interaction and subsequent PMN-mediated coronary endothelial dysfunction, which may be beneficial in ischemia-reperfusion and other inflammatory states.
我们研究了稳定的前列环素类似物他普前列素（2.5×10⁻⁸ M至1×10⁻⁷ M）对中性粒细胞与内皮细胞相互作用（即黏附）以及随后的血管收缩和内皮功能障碍的影响。他普前列素有效抑制了白三烯B4刺激的自体猫多形核（PMN）白细胞与分离的猫冠状动脉内皮的黏附。他普前列素还抑制了冠状动脉对白三烯B4刺激的PMN的血管收缩（p<0.01）。在用2 U/ml凝血酶或100 μM过氧化氢（H2O2）刺激的离体冠状动脉环中，未刺激的PMN与冠状动脉内皮的黏附显著增加，导致血管收缩和随后的内皮功能障碍。然而，他普前列素（1×10⁻⁷ M）显著减弱了未刺激的PMN对受刺激冠状动脉内皮的黏附。这种抗黏附作用有效减弱了PMN诱导的冠状动脉血管收缩（p<0.01），并显著减轻了随后以内皮源性一氧化氮（NO）丧失为特征的PMN诱导的内皮功能障碍（p<0.01）。因此，他普前列素对PMN与内皮细胞的相互作用以及随后PMN介导的冠状动脉内皮功能障碍具有深远的抑制作用，这在缺血再灌注和其他炎症状态下可能是有益的。
