Cyclic guanosine 3',5' monophosphate concentrations in pre-eclampsia: effects of hydralazine

To elucidate the role of the L-arginine:nitric oxide pathway in pregnancy and pre-eclampsia.

Pregnant women (nulliparous, age <25 years). Normotensive pregnancy (n=22) was defined when blood pressure remained at levels of <120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (n=22) had blood pressure measurements of >140/90 mmHg and proteinuria of >300 mg/l. Nonpregnant normotensive women (n=22) were studied as controls.

Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5' monophosphate (GMP),arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.

L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD 15.7) microM] were increased significantly (P<0.05) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) microM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) microM]. Concentrations of cyclic GMP in plasma and urine increased significantly (P<0.05) in women treated with hydralazine.

The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.