Effects of taprostene on neutrophil-endothelial interactions in isolated coronary arteries

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.