The influence of VIP and epoprostenol on platelet CD62P expression and primary haemostasis in vitro.
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.
Ludwig Boltzmann Institute of clincal Anaesthesiology and Intensive Care, Vienna, Austria. jochen.zwerina@univie.ac.at
Jochen
J
Zwerina
Harald
H
Landsteiner
Ursula
U
Leitgeb
Ivo
I
Volf
Ventzislav
V
Petkov
Michael
M
Zimpfer
Alex
A
Blaicher
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D005434:Flow Cytometry; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation / Q000187:drug effects; D010979:Platelet Function Tests / Q000379:methods; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D019007:P-Selectin; D016718:Arachidonic Acid; D014660:Vasoactive Intestinal Peptide; D000244:Adenosine Diphosphate; D011464:Epoprostenol