Role of Microsomal Prostaglandin E Synthase-1 (mPGES1)-Derived PGE2 in Patency of the Ductus Arteriosus in the Mouse

Prostaglandin E-2 (PGE(2)) plays a key role in the ductus arteriosus, prenatally by maintaining patency and postnatally by promoting tissue remodeling for closure. Here, by using near-term Mouse fetuses with (wild-type, WT) and Without microsomal PGE synthase-1 (mPGES1-/-), we have examined the importance of this enzyme for PGE(2) formation and function. mPGES1-/- ductus unlike WT ductus, contracted little, or not all, to indomethaein it, vitro. Coincidentally, as evident front responses to N-G-nitro-L-arginine methyl ester and zinc photoporphyrin, the mutant showed no significant enhancement of nitric oxide (NO)- and carbon monoxide (CO)-based relaxation. mPGES1 Suppression differs, therefore, from cyclooxygenase (COX) suppression, whether genetically or pharmacologically induced, where NO is markedly up-regulated. In vivo, the ductus was patent, albeit occasionally with a narrowed lumen, in all mPGES1-/- fetuses. Conversely, postnatal Closure progressed regularly in mPGES1-/- animals thanks to residual PGE(2) originating via mPGES2. We conclude that mPGES1 is critical for PGE(2) formation in the ductus but its loss does not entail compensatory upregulation of other relaxing mechanisms. Accordingly, all mPGES1 inhibitor stands Out as a prospective better tool, compared with the currently used COX inhibitors, for the management of premature infants with persistent ductus. (Pediatr Res 64: 523-527, 2008)