Investigation On The Relationship Between Placental Nitric Oxide System With The Pathogenesis Of Pregnancy-induced Hypertension

Objective By studying the changes of placental nitric oxide system in pregnancy-induced hypertension(PIH), which including the expression and activities of placental nitric oxide synthase (NOS^ the level of nitric oxide (NO) and cGMP, determine the relationship between placental nitric oxide system with the pathogenesis of PIH.Methods 40 placentae of PIH and 30 normal pregnant woman were studied. The localization and expression of endothelial nitric oxide synthase-mRNA (eNOSmRNA) were measured by in situ reverse transcription-ploymerse chain reaction(in situ RT-PCR) and image analysis, the activities expression of nitric oxide synthase in syncytiotrophoblast were measured by NADPH-diaphorase histochemistry and image analysis. The level of placental villous NO and cGMP were assayed by nitrate reductase and radioimmunoassay.Results l.The positive staining of eNOSmRNA were all evident in syncytiotrophoblast and endothelial cells of stem villous vessels in normotensive and PIH. The positive staining of eNOSmRNA in syncytiotrophoblast were weaker in PIH when compared with normotensive, but the positive staining of eNOSmRNA in endothelial cells of the stem villous vessels in PIH were greater than normotensive. eNOSmRNA was absent in endothelium of terminal villous capillary in normotensive, but was present in endothelium of terminal villouscapillary in PIH. By quantitative analysis, the level of eNOSmRNA expression in syncytiotrophoblast was decreased significantly in patients with PIH when compared with those of normal pregnant term woman(P < 0.01). There is no significant difference between mild PIH and normotensive (P > 0.05) , patients with moderate and severe PIH decreased significantly when compared with mild PIH(P < 0.05, P < 0.01), but there is no significant difference between moderate and severe PIH (P > 0.05 ) .2.The activities of NOS in placental syncytiotrophoblast was decreased significantly in patients with PIH when compared with those of normal pregnant woman(P < 0.01). There is no significant difference between mild PIH and normotensive(P > 0.05), patients with moderate and severe PIH decreased significantly when compared with mild PIH(P < 0.05, P < 0.01), but there is no significant difference between moderate and severe PIH (P > 0.05 ) . 3.A positive correlation was seen between NOS activities with the expression of eNOSmRNA in the placental syncytiotrophoblast of PIH and normotensive(r=0.906, 0.835) (P<0.01, P<0.01) .4.The level of placental villous NO and cGMP in PIH were decreased significantly when compared with normotensive(P < 0.05). Patients with moderate and severe PIH decreased significantly when compared with mild PIH(P < 0.05, P < 0.01), but there is no significant difference between moderate and severe PIH(P > 0.05).5.A negative correlation was seen between the level of placental villous nitric oxide with mean arteriol pressure (r=-0.514, P < 0.05) and a positive correlation was seen with newborn birth weigh ( r=0.751, P < 0.01) .Conclusion 1.eNOSmRNA is mainly present in placental villous syncytiotrophoblast. The overall and identical downregulation of placental nitricoxide system may be an important factor in the pathogenesis of PIH.2.It is inferred that L-argine and glyceryl trinitrate may treat PIH effectively.