HEME OXYGENASE AND NITRIC-OXIDE SYNTHASE IN THE PLACENTA OF THE GUINEA-PIG DURING GESTATION

Nitric oxide (NO) and carbon monoxide (CO) are novel gaseous chemical messengers that play key roles in cell function and cell-cell communic ation in many organ systems, including the cardiovascular system. Alth ough the presence of NO synthase (NOS) in the placenta and its role in the regulation of fetoplacental and uteroplacental blood flow are wel l established, little is known about placental expression and activity of heme oxygenase (HO), the enzyme that catalyses the oxidation of he me to CO, biliverdin and iron, during gestation. The objectives of thi s study were to elucidate the localization of HO-1 and HO-2 isoforms r elative to NOS III protein, and to determine the enzymatic activity of HO in the placenta of the guinea-pig during gestation. Placentae were obtained from pregnant guinea-pigs at gestational day (GD) 34, 50, 62 and full term (term, about GD 68). Immunohistochemical localization o f HO-1, HO-2 and NOS III protein was conducted using selective polyclo nal antibodies. HO activity was determined by using a gas chromatograp hic method to measure the rate of formation of CO from heme. Faint sta ining for HO-1 was observed in the adventitial layer of larger fetal b lood vessels of the placenta at GD 34. The intensity of this staining was higher at GD 30 and GD 62, and decreased at full term. Similar are as in serial sections of placentae obtained at these selected times du ring gestation exhibited lower staining intensity when incubated with anti-HO-2 antiserum. Placental HO activity was significantly increased (P<0.05) at GD 62 compared with GD 34, GD 50 and full term. NOS III ( endothelial constitutive NOS) staining was highest at GD 34, decreasin g thereafter, and was localized mostly to trophoblast lining maternal channels. The data demonstrate that, in the guinea-pig, placental HO a nd NOS differ in tissue localization during the second half of gestati on, with expression of HO protein and its catalytic activity being hig her during near-term pregnancy. In a preliminary immunohistochemical i nvestigation of the full-term human placenta, HO-1 protein was localiz ed primarily in the adventitial region of fetal blood vessels of stem chorionic villi. In view of the vasodilator action of CO and NO, the H O and NOS systems may play key roles in the regulation of placental ha emodynamics. (C) 1998 W. B. Saunders Company Ltd.