Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy.
Nitric oxide (NO) synthase (NOS) is active in the gravid uterus, and its activity decreases prior to the onset of parturition. We tested the hypothesis 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 later, uteri were analyzed for myometrial connexin 43 (Cx43) protein by immunoblotting 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 not 17 days gestation. Steady state mRNA concentrations were not changed at 24 h. NOS inhibition did not increase the concentrations of OTR, or PGHS protein, nor did it decrease maternal serum progesterone. We conclude that endogenous uterine NO from iNOS suppresses myometrial Cx43 gap junction protein 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.
Sladek
S M
SM
Magee-Womens Research Institute, Department of Obstetrics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Westerhausen-Larson
A
A
Roberts
J M
JM
D000818:Animals; D018031:Connexin 43 / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005865:Gestational Age; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D009215:Myometrium / Q000737:chemistry / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000032:analysis
D018031:Connexin 43; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester