Increased stimulation of uterine cGMP levels by atrial natriuretic peptidein human pregnancy

Objective In animals, endogenous factors such as nitric oxide and natriuret ic peptides have been shown to relax myometrium by inducing cyclic guanosin e monophosphate (cGMP) synthesis, via activation of soluble or particulate guanylate cyclase activity. However, the role of cGMP from soluble or parti culate guanylate cyclase in the human uterus is still unknown and was inves tigated here. Methods Myometrial samples of a total of 26 pregnant women at term (14 not in labor, 12 in labor) and 20 before term (ten not in labor, ten in labor) and of ten non-pregnant women were used for the study. Myometrial nitric ox ide synthase (NOS) activity was determined by conversion of L-arginine to L -citrulline. Furthermore, basal myometrial cGMP production and influence of the NOS substrate L-arginine and atrial natriuretic peptide (ANP) on cGMP production were measured. Results Myometrial NOS activity and basal cGMP production were independent of gestational age and labor state. Basal cGMP levels in non-pregnant women were higher than in pregnant women. Myometrial cGMP production was not inf luenced by L-arginine, but significantly increased by ANP. Increases in cGM P levels in response to ANP were significantly greater in the myometrium of pregnant as compared with nonpregnant women. Conclusions Our results question the hypothesis of an endogenous role of th e NO/cGMP system in inhibiting human uterine contractility during pregnancy . Moreover, the findings provide the first evidence for a possible role of an ANP-sensitive particulate guanylate cyclase-cGMP system in regulating hu man uterine contractility during pregnancy.