Reduction of lipopolysaccharide-induced cyclooxygenase-2 expression in diabetic arteries.

In order to clarify the effects of diabetes mellitus on induction of cyclooxygenase (COX)-2 and subsequent prostaglandin production in blood vessels, we investigated lipopolysaccharide (LPS)-induced COX-2 induction and prostacyclin production in aortic strips isolated from streptozotocin-induced diabetic rats and vehicle-injected control rats. The rats at 10 weeks after injection of streptozotocin had significantly lower body weights and higher serum glucose levels compared with those in the control rats. LPS stimulation resulted in a marked increase in the release of prostacyclin from the aortic strips. This increase was abolished in the presence of indomethacin or cycloheximide but was not affected by removal of the endothelium. In diabetic aortae, both LPS-induced prostacyclin production and COX-2 induction were diminished compared with the control aortae. No significant difference in COX-1 expression was observed between diabetic and control aortae. The diminution of LPS-induced COX-2 expression was also observed in alveolar macrophages isolated from diabetic rats. These results suggest that COX-2 expression and subsequent prostacyclin production in response to LPS are selectively attenuated in diabetic blood vessels.