DIFFERENTIAL REGULATION OF NITRIC-OXIDE IN THE RAT UTERUS AND CERVIX DURING PREGNANCY AND LABOR

The aim of this study was to determine if nitric oxide (NO) production and nitric oxide synthase (NOS) isoforms change within the uterus and cervix during pregnancy and labour either at term or preterm. NO prod uction was compared in the rat uterus and cervix of non-pregnant and p regnant rats on days 18-22 prior to labour, day 22 during delivery, 1 day post-partum and after treatment with either 10 mg onapristone or p rogesterone. Uterine NO synthesis, reflected in nitrite production, in creased during gestation (194.2 +/- 22.6 nmol/g on day 19) compared wi th the non-pregnant state (76.2 +/- 18.4 nmol/g, P < 0.05) and decreas ed during term labour and post-partum. Furthermore, injection of lipop olysaccharide (LPS) (100 mu g/rat i.p.) on day 20 of gestation resulte d in a significant increase in NO synthesis after 6 h. Conversely, cer vical NO synthesis and nitrite production was low in the nonpregnant ( 65.1 +/- 9.2 nmol/g) and pregnant animals on days 18-22 of gestation ( 53.2 +/- 9.0 nmol/g on day 22, P > 0.05), but markedly increased durin g term labour (139 +/- 28.6 nmol/g, P < 0.05). Treatment with the anti progestin onapristone suppressed uterine NO production and increased c ervical production while continuous administration of progesterone fro m day 19 had the opposite effect. LPS produced a significant increase in cervical NO production in both the pregnant (8-fold) and non-pregna nt (4-fold) states. All three known NOS isoforms (i.e. iNOS, nNOS and eNOS) were detected in the cervical samples but only two were present in the uterus (iNOS and eNOS). An increase in the presence of iNOS occ urred during labour at term compared with cervices collected from day 19. This was contrary to the measurements of the isoform in the uterus . Also, there was a similar increase of nNOS in the cervix during labo ur. This isoform seemed absent in the uterus during gestation. No sign ificant changes occurred in the abundance of eNOS in the cervix during labour at term compared with day 19. During preterm labour after onap ristone, iNOS concentrations increased significantly in the cervix. In order to examine whether the NO pathway plays a role in cervical ripe ning, the effects of the nitric oxide synthesis inhibitor L-nitro-argi nine methylester (L-NAME) on the duration of delivery and on cervical extensibility were also investigated. The duration of delivery was sig nificantly prolonged in L-NAME-treated rats compared with the control group (2.4-fold). Moreover, cervical extensibility decreased significa ntly (1.7-fold) after in-vitro incubation with L-NAME (P < 0.005). We conclude that the NO system may have an active role in the cascade of processes involved in preparing the uterus and cervix for parturition.