Regulation of prostacyclin production by vascular cells in in vitro and in vivo experimentals systems.

Prostacyclin (PGI2) is the major product of arachidonic acid (AA) metabolism in vascular cells. Its physiological role is linked to the cells' ability to produce PGI2 continuously in response to a variety of stimuli. Human endothelial cells or bovine smooth muscle cells in culture responded only once with PGI2 production to stimulation with AA, thrombin or ionophore A23187. Their refractoriness lasted about 6 hours. The same time was required by the cells to recover completely after inhibition of cyclooxygenase activity by aspirin. When the cells were repeatedly stimulated with AA in the presence of plasma no refractoriness was apparent. These results suggest that vascular cyclooxygenase is irreversibly self-inactivated during oxygenation with AA. As shown in other experimental systems, deactivation could be attributed to the attack on the enzyme by oxidizing species formed during AA conversion and the plasmatic free radical-scavenger systems could protect the cells from inactivation. Thus, vascular cells in an artificial medium cannot be stimulated continuously to produce PGI2, but this process is regulated by negative feed-backmechanisms. When the cells are stimulated in the presence of plasma i.e. in more physiological conditions, they are much less sensitive to inactivation.