EFFECT OF ELEVATED GLUCOSE ON CYCLIC-GMP AND EICOSANOIDS PRODUCED BY PORCINE AORTIC ENDOTHELIUM

The short-term effects of elevated glucose on cyclic GMP (cGMP) and ei cosanoid production in pig aortic endothelial cell monolayers was dete rmined by incubating cells in 5.5 mM or 44 mM glucose for 6 hours. Bra dykinin- or A23187-stimulated cGMP production was significantly reduce d in cells incubated in 44 mM glucose compared with 5.5 mM glucose. St imulation of cGMP levels with exogenously added nitric oxide (NO) was also decreased to a similar extent in cells exposed to 44 mM glucose. These data suggest that NO production stimulated by bradykinin or A231 87 was unchanged by elevated glucose. Assayed eicosanoids, including 6 -ketoprostaglandin (PG) F1alpha, PGE2, PGF2alpha, and 15(S)-hydroxy-(5 Z, 8Z, 11Z, 13E)-eicosatetraenoic acid, stimulated by bradykinin or A2 3187, were increased in cells exposed to 44 mM glucose. These eicosano id products formed from exogenously added arachidonic acid did not dif fer between cells incubated in 5.5 mM or 44 mM glucose. Hyperosmolar c oncentrations of mannose or sucrose had no effect on cGMP levels but d id mimic the effect of elevated glucose on eicosanoid production. Thes e data suggest that hyperglycemia in diabetes may interfere with NO-in duced guanylate cyclase activation but not NO production in the endoth elium and that increased phospholipase activity, secondary to hyperosm olarity, may account for elevated eicosanoid levels.