Nitric oxide donors stimulate prostaglandin F(2alpha) and inhibit thromboxane B(2) production in the human cervix during the first trimester of pregnancy.
Nitric oxide (NO) donors are capable of ripening the human cervix during pregnancy. The purpose of this study was to examine how NO donors may be involved in this process. Cervical biopsies were obtained from pregnant women randomized to receive isosorbide mononitrate (n = 10) or no treatment (n = 10) prior to suction termination. Enzyme-linked immunosorbent assays (ELISA) were performed on culture supernatant for interleukin (IL)-1, IL-6, IL-8, IL-10, IL-15, tumour necrosis factor-alpha, monocyte chemoattractant protein-1 and prostaglandin metabolites. Immunohistochemistry was performed to localize these cytokines, cyclooxygenase (COX)-1, COX-2 and prostaglandin dehydrogenase in cervical tissue and reverse transcription-polymerase chain reaction (RT-PCR) to identify COX-1 and COX-2 expression. Biopsies treated with the NO donor isosorbide mononitrate (IMN) produced significantly greater amounts of prostaglandin F(2alpha) in culture and lower amounts of thromboxane B(2) than controls (572.8 versus 34.9 pg/ml, P < 0.05; 53.3 pg/ml versus 530.9 pg/ml, P < 0.01 respectively). The release of other prostaglandins and of cytokines was not affected by treatment with NO. Inflammatory mediators were localized to cervical tissue and COX-1 and COX-2 expression was confirmed by RT-PCR. In conclusion, the mechanism of NO donor-induced cervical ripening during pregnancy may be mediated in part via increased prostaglandin F(2alpha) synthesis.
Ledingham
M A
MA
Department of Obstetrics and Gynaecology, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER, UK.
Denison
F C
FC
Kelly
R W
RW
Young
A
A
Norman
J E
JE
D001483:Base Sequence; D020070:Cervical Ripening / Q000187:drug effects / Q000502:physiology; D002584:Cervix Uteri / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015237:Dinoprost / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008565:Membrane Proteins; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000096:biosynthesis*
D016207:Cytokines; D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D013929:Thromboxane B2; D015237:Dinoprost; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate