Endothelial nitric oxide synthase in the human placenta: Regional distribution and proposed regulatory role at the feto-maternal interface

Abstract

Feto-placental vessels lack innervation, hence control of this circulation is dependent on locally produced and circulating vasoactive factors. Functional studies have presented evidence that nitric oxide, a potent vasodilator and platelet anti-aggregating agent, may be generated into the feto-placental circulation, contributing to control of vascular tone. In view of the absence of nerves supplying the placenta the source of NO is likely to be endothelial. We have therefore investigated the localization of endothelial constitutive nitric oxide synthase (ecNOS) in human normal full-term placentae, using immunocytochemistry, with rabbit antiserum to a synthetic peptide, corresponding to amino acid residues 1172–1186 of human and bovine ecNOS. On Western blots of partially purified NO synthase extracted from placenta, the peptide antiserum reacted exclusively with a single protein band of ≈ 135kDA. Immunoreactivity in tissue sections was localized to endothelium of umbilical artery and vein, and appeared uniform in sections at different levels along the cord. Staining in chorionic vessles was much more variable; it was present mainly in the larger vessels close to the cord where it had a patchy distribution. Staining was not seen in the endothelium of small feto-placental vessels. Strong immunoreactivity was evident in the syncytiotrophoblast of the placenta, although the intensity of staining was variable, being weaker along stem villi and strongest along terminal villi. The differential distribution and intensity of nitric oxide synthase immunoreactivity in the human placenta might indicate that locally produced, and in particular trophoblast-derived nitric oxide may play a pivotal role both in control of feto-placental vascular tone and as a platelet anti-aggregating agent in the utero-placental circulation.