Plasma cyclic GMP concentrations and their relationship with changes of blood pressure levels in pre-eclampsia

Background. One of the possible mechanisms responsible for pre-eclampsia is a loss of efficiency of the L-arginine-nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this nucleotid in the plasma of pre-eclamptic women. Subjects and methods. Sixteen pre-eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once a-day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP. Results. Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p<0.01) in pre-eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02+/-0.9 versus 4.8+/-0.76 versus 1.93+/-0.15 pmol . ml(-1), p<0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p<0.05) to 5.48+/-0.9 pmol . ml(-1). The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women. Conclusion. Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct index of the severity of pre-eclampsia.