INCREASED PROSTAGLANDIN-E GENERATION AND ENHANCED NITRIC-OXIDE SYNTHASE ACTIVITY IN THE NON-INSULIN-DEPENDENT DIABETIC EMBRYO DURING ORGANOGENESIS

Embryonic development, prostaglandin E (PGE) generation and nitric oxi de synthase (NOS) activity during organogenesis were evaluated in an e xperimental rat model of noninsulin-dependent diabetes (NIDD) generate d by neonatal administration of streptozotocin. Gross malformations we re detected in 5% of NIDD embryos and these embryos were all non-viabl e; in the other 95%, growth was retarded but no congenital abnormaliti es were found. Control embryos were all alive and not malformed. The N IDD Ii-day embryos secreted more PGE into the incubation medium than d id controls. The NO donor SIN-I increased PGE production in both contr ol and NIDD embryos. A NOS inhibitor (L-NMMA) reduced PGE generation i n both experimental groups, suggesting a modulatory role of NO on embr yonic PGE production. Activity of NOS was higher in NIDD 11-day embryo s than in controls. Treatment in vivo of control and NIDD rats (Days 7 -11 of gestation) with a NOS inhibitor (L-NAME; 5 mg kg(-1) i.p.) redu ced embryonic PGE production and induced a higher resorption rate and an increase in neural-tube defects. The results suggest that NO modula tes PGE generation in the organogenetic embryo. In the NIDD model, ove rproduction of NO is observed, this NO probably enhancing embryonic PG E production. The relationship between PGE generation and the appearan ce of congenital abnormalities is discussed.