Zwerina Jochen, Landsteiner Harald, Leitgeb Ursula, Volf Ivo, Petkov Ventzislav, Zimpfer Michael, Blaicher Alex
Ludwig Boltzmann Institute of clincal Anaesthesiology and Intensive Care, Vienna, Austria.
Platelets. 2004 Feb;15(1):55-60. doi: 10.1080/0953710032000159294.
Human vasoactive intestinal peptide (VIP) and epoprostenol (prostacyclin) have vasodilatative effects in the pulmonary circulation. Both VIP and epoprostenol are successfully used to treat pulmonary hypertension in humans and experimental animal models. The positive effects of epoprostenol on the course of this disease are achieved through vasodilatation and inhibitory effects on platelet activity. Since VIP also binds specifically to platelets, we compared the in vitro effects of VIP and epoprostenol on platelet P-Selectin (CD62P) expression and primary haemostasis. Anti-aggregative effects of VIP (10(-6) mol and 10(-8) mol) and epoprostenol (50, 5 and 0.5 ng/ml) on platelets were determined by agonist-induced CD62P expression and in vitro bleeding time (PFA-100 trade mark system). Blood from healthy individuals was either incubated with epoprostenol, VIP or saline control and was analysed by whole blood flow cytometry and the PFA-100 trade mark. Prior to flow cytometric analysis, the platelets were stimulated with either arachidonic acid (AA) or adenosine diphosphate (ADP). Whole blood flow cytometry analysis showed that epoprostenol inhibited dose-dependently agonist-induced CD62P expression, whereas VIP did not inhibit CD62P expression. PFA analysis revealed substantial closure time prolongation by epoprostenol and again no effects of VIP. These results indicate that VIP, in contrast to epoprostenol, has no effect on platelet CD62P expression and primary haemostasis.
人血管活性肠肽（VIP）和依前列醇（前列环素）在肺循环中具有血管舒张作用。VIP和依前列醇均成功用于治疗人类和实验动物模型中的肺动脉高压。依前列醇对该疾病病程的积极作用是通过血管舒张和对血小板活性的抑制作用实现的。由于VIP也能特异性结合血小板，我们比较了VIP和依前列醇对血小板P-选择素（CD62P）表达和初级止血的体外作用。通过激动剂诱导的CD62P表达和体外出血时间（PFA-100商标系统）测定了VIP（10⁻⁶mol和10⁻⁸mol）和依前列醇（50、5和0.5 ng/ml）对血小板的抗聚集作用。将健康个体的血液与依前列醇、VIP或生理盐水对照孵育，然后通过全血流式细胞术和PFA-100商标进行分析。在流式细胞术分析之前，用花生四烯酸（AA）或二磷酸腺苷（ADP）刺激血小板。全血流式细胞术分析表明，依前列醇剂量依赖性地抑制激动剂诱导的CD62P表达，而VIP不抑制CD62P表达。PFA分析显示依前列醇可显著延长封闭时间，而VIP再次无作用。这些结果表明，与依前列醇不同，VIP对血小板CD62P表达和初级止血无影响。
