PHYSIOLOGICAL DILATION OF UTEROPLACENTAL ARTERIES IN THE GUINEA-PIG DEPENDS ON NITRIC-OXIDE SYNTHASE ACTIVITY EXTRAVILLOUS TROPHOBLAST

The trophoblast invasion of uteroplacental arteries in the guinea pig has been studied by means of electron microscopy and immunohistochemis ty. To identify trophoblast cells, smooth muscle cells, and endothelia l cells, antibodies against cytokeratins, smooth muscle myosin, desmin , and vimentin were employed. Furthermore, the immunohistochemical exp ression patterns of nitric oxide synthase isoforms (eNOS, mNOS and bNO S) were studied and were compared with the enzyme histochemical staini ng for NADPH-diaphorase. Dilation of uteroplacental arteries begins pr ior to day 30, when trophoblast cells that coexpress endothelial and m acrophage nitric oxide synthase can be found in the vicinity of the ve ssels and replace the surrounding peritoneal mesothelium. Trophoblast invasion of the arterial walls and the subsequent wall destruction are only secondary effects. Starting around day 50, the final steps of pr egnancy-dependent vessel modifications involve intraarterial trophobla st adhesion to the endothelium and subsequent replacement of the endot helium by the trophoblast cells. These may centrifugally invade the ve ssel media eventually forming intraluminal plugs. These findings led u s to the conclusion that in the guinea pig pregnancy-induced physiolog ical dilation of the uteroplacental arteries is due to the effect of n itric oxide rather than being caused by trophoblast-induced media dest ruction.