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.
Lefer
A M
AM
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Murohara
T
T
Buerke
M
M
D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D002317:Cardiovascular Agents / Q000378:metabolism / Q000494:pharmacology*; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011465:Prostaglandins, Synthetic / Q000378:metabolism / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D002317:Cardiovascular Agents; D011465:Prostaglandins, Synthetic; D007975:Leukotriene B4; D009569:Nitric Oxide; C039188:taprostene; D006861:Hydrogen Peroxide; D011464:Epoprostenol; D013482:Superoxide Dismutase; D013917:Thrombin