The acute effect of in vitro deendothelialization on the production of prostacyclin (PGI2) by the rabbit aorta has been investigated. The effectiveness of removing endothelium by rubbing it against filter paper or scraping it with a scalpel was demonstrated by scanning electron microscopy and en face examination after silver staining. Endothelium removal produced an immediate stimulation of PGI2 release, resulting in 408% of the control after rubbing and 367% of the control after scraping, during the first 30-min period of incubation. This increased production of PGI2 gradually declined over time to reach values similar to the control after 2h. At that time, the deendothelialized aorta was totally unresponsive to the stimuli that increase PGI2 release in the intact aorta (acetylcholine, ADP, ionophore A23187, and arachidonic acid). The enhanced production of PGI2 in the deendothelialized aorta was associated with an increased release of free arachidonic acid (353% of the control): in contrast with PGI2, this stimulation was maintained for at least 150 min. A transient exposure of the deendothelialized aorta to ibuprofen (250 microM) was followed by a rebound of PGI2 production, which was also prolonged by BW-755C (3-10 microM). In conclusion, removal of the endothelium triggered an immediate and sustained mobilization of free arachidonic acid in the rabbit aorta: the resulting increase of PGI2 production was short-lived, probably as a consequence of cyclooxygenase self-inactivation. Our results indicate that the subendothelium has a significant capacity to produce PGI2, but that this capacity is expressed only briefly.
J M Boeynaems, N Galand, P Ketelbant