PROSTACYCLIN RELEASE FROM CULTURED AND EXVIVO BOVINE VASCULAR ENDOTHELIUM - STUDIES WITH THROMBIN, ARACHIDONIC-ACID, AND IONOPHORE A23187

Abstract

Prostacyclin [PGI2] release from systemic and pulmonary endothelium was evaluated in cultured cell monolayers and in an ex vivo vascular segment model in which the endothelium remains in contact with subendothelial structures. The effect of exposure to arachidonic acid, ionophore A23187 [calcimycin], and thrombin on PGI2 release was assessed. Arachidonic acid elicited PGI2 release in a dose-dependent fashion. Ionophore also stimulated bovine systemic endothelium to release PGI2. Thrombin-endothelial cell interactions were examined extensively. Unlike umbilical venous endothelium, systemic and pulmonary bovine endothelium did not rlease PGI2 following exposure to thrombin. Exposure to thrombin also failed to evoke the release of [3H]-arachidonate metabolites from the bovine endothelial cell preparations. The presence of high affinity binding sites for thrombin (Kd = 9.5 .times. 10-9 M) on the bovine endothelium suggests that either thrombin binding is causally unrelated to PGI2 release or that the bovine cells lack mediators required for thrombin to exert its effects.