Effect of asymmetric dimethyl arginine on nitric oxide synthase activity in normal and pre-eclamptic placentae

An endogenous inhibitor of nitric oxide synthase (NOS), N-G,N(G)dimethylarginine. (asymmetric dimethylarginine, ADMA), which is present in human plasma and urine, has been reported to be elevated in the plasma of women with pre-eclampsia. As ADMA inhibition may contribute to reduced placental NOS activity observed in pre-eclampsia, the aim of this study was to compare the effects of ADMA on placental NOS activity from pre-eclamptic and normal pregnancies (gestational ages 38.4+/-0.9 and 38.3+/-0.3 weeks respectively). NOS activity was determined by measuring the conversion of [H-3]L-arginine to [H-3]L-citrulline in homogenates of normal and pre-eclamptic placentae in the absence and presence of increasing concentrations of ADMA (1-100 mu M) The IC50 for ADMA for the pre-eclamptic placentae (22.1+/-2.1 mu M, n = 6) was not significantly different from that for the normal placentae (18.8+/-1.4 mu M, n = 6). When ADMA and L-arginine in homogenates was removed by ion exchange chromatography and exogenous L-arginine replaced (32 mu M), the IC50 for the pre-eclamptic placentae (19.5+/-1.8 mu M, n = 6) was not significantly different than that for the normal placentae (20.9+/-1.0 mu M, n = 6), and NOS activity in the absence of endogenous and exogenous ADMA was still reduced in pre-eclamptic placentae. These results provide no evidence that the sensitivity of placental NOS to ADMA is affected by pre-eclampsia, or that placental ADMA contributes to the reduction of placental NOS in pre-eclampsia.