Treatment Of NO Deficiency-induced Gestational Hypertension Using Combination Of Magnesium Sulfate With L-arginine

Objective:1,To investigate the localization and expression of placenta growth factor (P1GF) and the soluble vascular endothelial growth factor receptor-1(sVEGFR-1/ sFlt-1) in the placenta tissue of the mice induced by N-nitro-arginine methyl ester (L-NAME )and discuss their roles in the pathogenesis of hypertensive disorder complicating pregnancy.2,To study the effects and mechanisms of L-arginine(L-Arg), magnesium sulfate and their combination on mice with L-NAME-induced gestational hypertension and discuss their roles in the pathogenesis of hypertensive disorder complicating pregnancy.Medthods:1,After subcutaneous injection of three different doses of L-NAME, to detect the level of blood pressure and urine protein, as well as the localization and expression of P1GF and sFlt-1 in the placenta tissue applying immunofluorescence assay, immunohistochemistry assay and Western Blot assay , and then to choose the suitable model mice.2,The gestational hypertension mice were treated by L-arginine, magnesium sulfate or their combination. To compare the effect of different therapies by observing the level of blood pressure and urine protein,the level of NO and NOS in the plasma and placenta and the expression of P1GF and sFlt-1 in the placenta tissue.Results:1,Compared with normal mice, the level of blood pressure and urine protein were significantly higher in L-NAME-induced gestational hypertension mice (P<0.05,P<0.05).Histopathological characteristics of placenta and kidney were similar to those of hypertensive disorder complicating pregnancy.2,Immunohistochemistry staining and Immunofluorescence assay show that P1GF,sFlt-1 protein locate in the trophoblast cell and vascular endothelial cell of placental villus. Compared with normal mice, in L-NAME groups, the expression of P1GF was relatively lower and the expression of sFlt-1 was relatively higher. There is a decrease tendency for expression of P1GF and a increase tendency for expression of sFlt-1 with the increasing L-NAME dose.3,After therapy, the level of blood pressure and urine protein in L-Arg group,magnesium sulfate group and (L-Arg+magnesium sulfate) group were significantly lower than model group(P<0.01, P<0.01),but higher than normal control group(P<0.05, P<0.05).4,The NO concentration of plasma and placenta in L-Arg group and (L-Arg+magnesium sulfate) group were higher than model group (P<0.05, P<0.01). The NOS activity of plasma and placenta in (L-Arg+magnesium sulfate) group was higher than model group and magnesium sulfate group(P<0.05, P<0.05).5,The AOD value shows that in (L-Arg+magnesium sulfate) group the expression of P1GF protein was higher than model group(P<0.05)and the expression of sFlt-1 protein was lower than model group(P<0.05).Conclusion:1,By inhibiting the NO synthesis could establish gestational hypertension animal model.The abnormal expression of NO may be involved in the pathogenesis of hypertensive disorder complicating pregnancy.2,The decreased expression of P1GF and overexpression of sFlt-1 may be associated with pathogenesis of hypertensive disorder complicating pregnancy.3,L-arginine,magnesium sulfate and their combination therapy all may decrease the level of urine protein and blood pressure in model mice, promoting NO synthesis and regulating the expression P1GF/ sFlt-1.The incidence fetal death in uterus decreased remarkably in the treatment group by improving uteroplacental circulation and the growth of fetus and placenta.But the combination can offer a better therapeutic effect than the treatment with single agent.