Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia

Objectives. To study endogenous nitric oxide (NO) synthesis inhibitors in preeclampsia by measuring asymmetric dimethyl arginine (ADMA) and arginine. Study design. Blood samples for measurement of plasma concentrations of ADMA and arginine were obtained antepartum (range 32-39 weeks gestation), 3-5 days postpartum and 3 months postpartum from 12 pregnant women with severe preeclampsia and from a normotensive pregnant control group (n=12). Results. During the third trimester, plasma ADMA was elevated (p<0.05) in the preeclampsia patients (0.55+/-0.02 mu mol/l) compared to the normotensive pregnant controls (0.36+/-0.01 mu mol/l). Since plasma arginine levels did not differ between preeclamptic and normotensive control women (80.7+/-5.8 mu mol/l) and 74.5+/-3.8 mu mol/l respectively), the plasma arginine/ADMA ratio was lower (p<0.05) in the preeclamptic group (145.6+/-10.5) compared to the normotensive controls (211.0+/-14.3). Three days post partum there was an increase (p<0.05) in plasma ADMA in both the preeclamptic (0.67+/-0.03 mu mol/l) and the normotensive control group (0.64+/-0.03 mu mol/l). This was accompanied by a rise (p<0.05) in plasma arginine levels in both the preeclamptic patients (112.9+/-10.5 mu mol/l) and the normotensive control group (121.7+/-9.6 mu mol/l). At this lime point there was no difference in plasma arginine/ADMA ratio between the groups. Three months postpartum, plasma ADMA levels were slightly lower in both groups compared to the postpartum values (preeclampsia: 0.56+/-0.03 mu mol/l, normotensive pregnant control: 0.52+/-0.03 mu mol/l). Conclusion. Elevated circulating ADMA concentrations in combination with low plasma arginine levels may be of pathophysiological importance in pregnancies complicated with preeclampsia.