The conversion of arachidonic acid to vasoactive prostanoids including prostacyclin, prostaglandins and tromboxanes is mediated by cycloxygenase (COX). Two isoforms of enzyme have been shown: a constitutive (COX-1) and an inducible form (COX-2). Products of the arachidonic acid metabolism may be involved in the impairment of endothelium-dependent vasodilatation observed both in experimental models and in patients with diabetes mellitus. To determine the effect of hyperglycemia on COX-1 and COX-2 expression, human aortic endothelial cells (HAEC) were exposed to normal (5.5mM) and high (22.2mM) concentrations of glucose for 5 days. Cells were also treated with mannitol (22.2 mM) to rule out an effect due to osmolality changes. COX-1 and COX-2 mRNA and protein expressions were analyzed by Southern and Western blotting, respectively. Treatment with high glucose was associated with a two-fold increase of both COX-2 mRNA (P<0.05) and protein levels (P<0.05), whereas no changes were observed for COX-1. Moreover high concentration of mannitol did not exert any significant effect. The present study demonstrates that both isoforms of COX are normally expressed in HAEC, but only COX-2 was stimulated after exposure to high glucose. The results of the present study may provide molecular basis to understand hyperglycemia-induced endothelial dysfunctio
