Susceptibility of diabetic rat aorta to self-deactivation during prostacyclin synthesis

The ability of aortic rings to produce PGI₂ markedly decreased in streptozotocin-induced diabetic rats when compared with age-matched controls. Arachidonic acid dose-dependently stimulated the production of PGI₂ both in normal and diabetic rat aorta during 5 min incubation. The deficiency in PGI₂ production in diabetic rat aorta was temporarily corrected by the addition of 5–20 μM of arachidonic acid. However, when aortic rings were incubated over a period of 10 min in the presence of arachidonic acid, the ability of PGI production in diabetic rats markedly decreased. Repeated exposures A aortic rings to arachidonic acid also markedly reduced PGI₂ production in diabetic rats. PGI₂ production in diabetic rat aorta was inactivated more readily than in normal rat aorta by pre-incubation with t-butyl hydroperoxide. Phenol had a protective effect on incubation-induced inactivation of PGI₂ generating activity in diabetic rat aorta. Serum markedly stimulate PGI₂ synthesis in normal and diabetic rat aorta. The serum activity in diabetic rats was less potent than in normal rats. Melittin and dipyridamole were effective in stimulating PGI₂ release from diabetic rat aorta.

These results suggest that enzymes in the aorta involved in PGI₂ synthesis from released arachidonic acid are susceptible to self inactivation in diabetic rats during the metabolism of arachidonic acid. This may contribute to the defect of PGI₂ synthesis in diabetic rat aorta in addition to the decreased availability of the substrate.