Endogenous nitric oxide suppresses pat myometrial connexin 43 gap junctionprotein expression during pregnancy

Nitric oxide (NO) synthase (NOS) is active in the gravid uterus, and its ac tivity decreases prior to the onset of parturition. Mle tested the hypothes is that NO helps maintain uterine quiescence by suppressing the expression of genes necessary for parturition. Pregnant rats (18 days gestation) were treated with inducible NOS (iNOS) inhibitor N-iminoethyl-L-lysine (NIL) or endothelial NOS inhibitor nitro-L-arginine methyl ester (L-NAME); 24 h late r, uteri were analyzed for myometrial connexin 43 (Cx43) protein by immunob lotting and mRNA by Northern analysis. Myometrial oxytocin receptors (OTR) were measured by radioligand binding, and decidual prostaglandin H synthase (PGHS) protein by immunoblotting. Uterine NOS blockade was verified by NOS activity assay. We found that NIL, but not L-NAME, significantly increased myometrial Cx43 protein to parturitional levels with treatment at 19 but n ot 17 days gestation. Steady state mRNA concentrations were not changed at 24 h, NOS inhibition did not increase the concentrations of OTR, or PGHS pr otein, nor did it decrease maternal serum progesterone. We conclude that en dogenous uterine NO from iNOS suppresses myometrial Cx43 gap junction prote in expression during rat pregnancy. Although the exact mechanism is unknown , an increase of uterine wall stretch due to inhibition of relaxation could account for increased Cx43 gene transcription.