Nitric oxide synthase activity in pregnant rabbit uterus decreases on the last day of pregnancy

Sladek, Stephen M.; Regenstein, Anne; Lykins, David L.; Roberts, James M.

doi:10.1016/0002-9378(93)90295-t

Cited by 152 publications

(80 citation statements)

References 22 publications

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“…It is widely accepted that the increased production of NO by the pregnant myometrium serves to maintain uterine relative quiescence and the decrease of NO production close to term may be one of the trigger signals to start delivery activity (7,8). The up-regulated expression of iNOS was demonstrated in myometrial smooth muscle of pregnant rats (7,8), rabbits (17), guinea pigs (14), and humans (18), although the role of NO in human myometrium was questioned (19). In our experiments, expression of iNOS mRNA reached a maximum level on day 17 of gestation and was decreased on day 21 before the delivery, which confirms the previous data (7).…”

Section: Discussionmentioning

confidence: 99%

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

et al. 2004

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Abstract. Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine / nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident.

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Section: Discussionmentioning

confidence: 99%

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

et al. 2004

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“…(Subsequent studies have verified that rat myometrial smooth muscle iNOS expression is upregulated in pregnancy and falls at term [18].) Upregulation of NOS activity in the uterus with pregnancy has also been demonstrated by others both in rats (19) and in rabbits (20), but it was not found in the guinea pig (21). In humans, there is evidence of endogenous NO production by the uterus in 24-h tissue cultures (15).…”

Section: Introductionmentioning

confidence: 84%

“…It is unclear whether the increases in uterine NOS activity that have been observed are due to changes in myometrial or decidual NO production (20). Since NO has an estimated diffusion range of 100 m or less (22), we hypothesized that NO should be produced within the myometrium to suppress organized uterine contractions.…”

Section: Introductionmentioning

confidence: 98%

A decline in myometrial nitric oxide synthase expression is associated with labor and delivery.

Bansal¹,

Goldsmith²,

He³

et al. 1997

J. Clin. Invest.

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The mechanisms that maintain relative uterine quiescence during pregnancy remain largely unknown. A possible role for nitric oxide has recently emerged, however, the expression of nitric oxide synthase within human myometrium at midgestation, a time when the uterus is normally quiescent, has not been investigated. The purpose of this study was to identify cell types in human myometrium that contain inducible nitric oxide synthase (iNOS), and to examine changes in its expression during pregnancy and labor. We found that iNOS is expressed in smooth muscle cells of pregnant myometrium. Expression of iNOS was highest in myometrium of preterm not-in-labor patients. At term, iNOS expression fell by 75%, and was barely detectable in preterm in-labor or term in-labor specimens. There was no staining in the myocytes of nonpregnant myometrium. Western blotting also revealed a similar pattern of changes in iNOS expression. In summary, iNOS expression in the myocytes of human myometrium is increased greatly during pregnancy, and declines towards term or with labor. Significantly, preterm inlabor patients also had a large decline in iNOS expression. These data suggest that changes in myometrial iNOS expression may participate in the regulation of uterine activity during human pregnancy.

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“…Inducible NOS expression can also be detected in a variety of other cell types after cytokine stimulation in vitro, but the expression of iNOS in normal tissues is relatively rare (28). Reported examples of tissues normally expressing iNOS include the rat uterus, the pregnant rabbit uterus, and large airways in humans (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

Voorhis

Moore²,

Strijbos³

et al. 1995

J. Clin. Invest.

117

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Nitric oxide is reportedly involved in the regulation of several ovarian processes, yet the isoforms of nitric oxide synthase (NOS) expressed in the ovary are unknown. Our purpose was to identify and localize NOS isoenzymes in the rat ovary and to examine if mRNA expression of NOS isoenzymes change after gonadotropin stimulation. Using reverse transcriptase-PCR, we demonstrated that inducible (iNOS) and endothelial (eNOS), but not neuronal, NOS mRNAs are expressed in the ovary. In a gonadotropin-stimulated rat model, unstimulated ovaries had the highest levels of iNOS mRNA as quantified by ribonuclease protection assay. After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slightly in ovaries containing copora lutea. In situ hybridization studies localized iNOS to granulosa cells of secondary follicles and small antral follicles. Western blots of unstimulated ovaries demonstrated iNOS protein. In contrast to iNOS, eNOS mRNA levels, determined by quantitative PCR, increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase. eNOS protein was localized to blood vessels in the ovary by immunohistochemistry. We conclude that two isoforms of NOS are expressed in the ovary and the mRNA levels for these isozymes are differentially regulated. (J. Clin. Invest. 1995. 96:2719-2726

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Nitric oxide synthase activity in pregnant rabbit uterus decreases on the last day of pregnancy

Cited by 152 publications

References 22 publications

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

Expression of iNOS mRNA and Inhibitory Effect of NO on Uterine Contractile Activity in Rats Are Determined by Local Rather Than Systemic Factors of Pregnancy

A decline in myometrial nitric oxide synthase expression is associated with labor and delivery.

Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo.

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