Nitric oxide stimulation of cGMP accumulation in myometrial cells from pregnant women is antagonized by oxytocin.

Abstract

The role of cGMP in the myometrium of pregnant women is not completely known. We have previously shown in guinea pig, monkey and man that NO-induced relaxation of oxytocin-induced contractions is independent of cGMP accumulation. To approach an understanding of the role of cGMP in myometrium, we have developed smooth muscle cell cultures from pregnant women undergoing caesarian section at term. Cells, grown in standard media containing progesterone, express smooth muscle cell markers and are used within five doublings. Cells stimulated with NO donors increase their cGMP levels nearly 100 fold (basal = approximately 9 pmol/mg protein). In the presence of oxytocin (OT; 1 microM), cGMP accumulation in the presence of NO (100 microM) is significantly blunted (25 fold). Cyclic GMP-degradation is inhibited by the presence of the phosphodiesterase inhibitor zaprinast; suggesting that the ability of OT to attenuate cGMP accumulation is unlikely to be due to degradation. We propose that the elevation of intracellular calcium following the addition of OT suppress the activity of a calcium-sensitive guanylyl cyclase. The diminution of cGMP synthetic potential in myometrial cells from pregnant women is consistent with the absence of a role for cGMP in the NO-induced relaxation of uterine muscle.