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 microM of arachidonic acid. However, when aortic rings were incubated over a period of 10 min in the presence of arachidonic acid, the ability of PGI2 production in diabetic rats markedly decreased. Repeated exposures of 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 stimulated 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.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001095:Arachidonic Acids; D010636:Phenols; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol