Nitric oxide in the human uterus

Norman, Jane E.; Cameron, Iain

doi:10.1530/ror.0.0010061

Cited by 70 publications

(11 citation statements)

References 28 publications

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Section: Discussionmentioning

confidence: 99%

“…The eNOS expression in the sheep placenta has been demonstrated to elevate during early pregnancy [20]. The expression of a high amount of iNOS mRNA has been reported in the human decidua and chorionic villi in the first trimester of pregnancy, suggesting that iNOS plays an important role for successful placentation and embryo development during early pregnancy [21,22].In the human placenta, NOS isoenzymes are also found in the placental vessels. The iNOS is distributed in arteriolar smooth muscle and the venous endothelium of umbilical vessels, and eNOS is present in the endothelial cells of umbilical and chorionic vessels [23][24][25][26].…”

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confidence: 99%

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Expression and Localization of NO Synthase Isoenzymes (iNOS and eNOS) in Development of the Rabbit Placenta

Khan

Kusakabe

Wakitani

et al. 2012

Journal of Reproduction and Development

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Abstract. Nitric oxide synthase (NOS) is a key regulator of angiogenesis and embryogenesis in the mammalian reproductive process. Here, we attempted to clarify the expression and localization of inducible and endothelial NOS (iNOS and eNOS) in the developing rabbit placenta. Real-time RT-PCR analysis indicated that iNOS mRNA was significantly upregulated till the complete development of the placenta (d18), and then significantly decreased at the end of fetal growth stage (d28) during successful pregnancy. The eNOS mRNA was also enhanced in the pregnant uteri and gradually decreased near the term of pregnancy. Western blot analysis also showed elevation of the iNOS and eNOS protein levels during the course of successful pregnancy till the functional maturation of the placenta (d18). Immunohistochemical study revealed distinct localizations of iNOS along the radial arteries and eNOS at the spiral arteries and arterial sinuses in the developing placenta. This may reflect that iNOS and eNOS participate in pregnancy success through placentation-specific vascular formation and by supporting adequate blood circulation in the rabbit placenta. Key words: eNOS, iNOS, Rabbit placenta, Vascular formation (J. Reprod. Dev. 58: [231][232][233][234][235][236] 2012) I n pregnant mammals, the placenta acts as exchange interface for nutrients and waste products between the fetal and maternal circulation. The placenta is a very fast growing tissue with corresponding high metabolic demand from the embryo or fetus that requires an active blood supply and rapid vascular development [1][2][3]. Failure of placental growth during early and mid pregnancy is directly associated with inadequate uterine and umbilical blood flow, which adversely affects transportation of fetal nutrients [4]. Extensive increase of the transplacental exchange during the last half of gestation is closely dependent upon the dramatic growth of the vascular architecture and the resultant large volume of uterine and umbilical blood flow [1].Nitric oxide (NO), a multifunctional biomolecule, is produced from the essential amino acid L-arginine via nitric oxide synthase (NOS), which is classified into the calcium-independent or constitutive calcium/calmodulin-sensitive isoforms. The former is represented by inducible NOS (iNOS), and the latter is represented by the endothelial and neuronal NOS (eNOS and nNOS) [5]. NO plays crucial roles in the mediation of a wide variety of physiological processes including vasodilation, angiogenesis, platelet aggression, immune functions, connective tissue remodeling and smooth muscle activity [6]. iNOS and eNOS are known to dynamically regulate normal physiological events during successful pregnancy such as ovulation, implantation, trophoblast invasion, placental formation, fetal development and delivery [7][8][9].In the developing placenta, specific vascular formation occurs through the processes of destruction of preexisting vessels, de novo angiogenesis and convergence of blood path in association with the invitation of plenty ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expression and Localization of NO Synthase Isoenzymes (iNOS and eNOS) in Development of the Rabbit Placenta

Khan

Kusakabe

Wakitani

et al. 2012

Journal of Reproduction and Development

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“…Nitric oxide is hypothesized to contribute to the maintenance of pregnancy, by increasing uterine blood flow [2,3], maintaining myometrial quiescence [4][5][6], and others. The major effect of nitric oxide on cell function is mediated through the activation of soluble guanylyl cyclase, which generates guanosine 3',5'-cyclic monophosphate (cGMP) as an intracellular second messenger [7].…”

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confidence: 99%

Expression of Nitric Oxide Synthase Isoforms in the Human Placenta Is Not Altered by Labor

et al. 2003

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Abstract. Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 ± 0.1652 (eNOS/GAPDH, mean ± SEM) and 12.8 ± 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 ± 0.2042 (eNOS/GAPDH) and 11.4 ± 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 ± 0.2436 (iNOS/GAPDH) and 10.7 ± 2.1 AU respectively, similar to those not in labor, 1.9254 ± 0.8004 (iNOS/GAPDH) and 13.3 ± 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) cocentration in the placental tissues in labor was 23.6 ± 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 ± 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.

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“…Some effects of NO such as those of GSNO on mitochondrial function require concentrations from 100 to 500 M (Cleeter et al, 1994). The relaxant actions of NO donors in smooth muscle are half-maximal in the 1 to 10 M range (Norman and Cameron, 1996;Buxton et al, 2001;Modzelewska and Kostrzewska, 2005), although, Fig. 2.…”

Section: Discussionmentioning

confidence: 99%

Uterine Smooth MuscleS-Nitrosylproteome in Pregnancy

Ulrich¹,

Quillici²,

Schegg³

et al. 2011

Mol Pharmacol

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The molecular mechanisms involved in uterine quiescence during gestation and those responsible for induction of labor are not completely known. Nitric oxide relaxes uterine smooth muscle in a manner disparate from that for other smooth muscles because global elevation of cGMP after activation of soluble guanylyl cyclase does not relax the muscle. S-Nitrosylation, the covalent addition of an nitric oxide (NO) group to a cysteine thiol is a likely mechanism to explain the ability of NO to relax myometrium. This work is the first to describe the myometrial S-nitrosylproteome in both pregnant and nonpregnant tissue states. Using the guinea pig model, we show that specific sets of proteins involved in contraction and relaxation are S-nitrosylated in laboring and nonlaboring muscle and that many of these proteins are uniquely S-nitrosylated in only one state of the tissue. In particular, we show that S-nitrosylation of the intermediate filament protein desmin is significantly increased (5.7-fold, p Ͻ 0.005) in pregnancy and that this increase cannot be attributed solely to the increase in protein expression (1.8-fold, p Ͻ 0.005) that accompanies pregnancy. Elucidation of the myometrial S-nitrosylproteome provides a list of mechanistically important proteins that can constitute the basis of hypotheses formed to explain the regulation of uterine contraction/relaxation.

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Nitric oxide in the human uterus

Cited by 70 publications

References 28 publications

Expression and Localization of NO Synthase Isoenzymes (iNOS and eNOS) in Development of the Rabbit Placenta

Expression and Localization of NO Synthase Isoenzymes (iNOS and eNOS) in Development of the Rabbit Placenta

Expression of Nitric Oxide Synthase Isoforms in the Human Placenta Is Not Altered by Labor

Uterine Smooth MuscleS-Nitrosylproteome in Pregnancy

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