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

Okawa, Toshiaki; Asano, Kimisato; Takahashi, Hidenori; Hashimoto, Shinichi; Anbe, Hiroshi; Sato, Akira; Gafield, R. E.

doi:10.1254/jphs.fpj04003x

Cited by 12 publications

(12 citation statements)

References 28 publications

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“…In our investigation, LPS clearly stimulated NOx production in the pregnant uterus. l ‐arginine and DEA/NO have been demonstrated to inhibit spontaneous contractions of pregnant rat uterine tissues at mid‐gestation, 10–12 and the data presented here confirm this conclusion. LPS significantly attenuates uterine contractions in uterine rings induced by all three NO‐related agents in pregnant mice, because PG production was increased by LPS.…”

Section: Discussionsupporting

confidence: 84%

“…It has been demonstrated that an l ‐arginine–NO–cGMP pathway exists in myometrium and that it is upregulated during pregnancy to maintain relative uterine quiescence until term 10–12 . Furthermore, there are reports showing that decreasing NO production may induce preterm delivery 10,23,28 .…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that NO is involved in the relaxation of smooth muscles including myometrium. The NO‐dependent mechanism is important in maintaining relative uterine quiescence during pregnancy and in preventing preterm labor, while a decrease in myometrial sensitivity to NO contributes to the onset of labor 11,12 . Clinically, nitroglycerin, an NO donor, has been demonstrated to provide life‐saving uterine relaxation for difficult breech extraction and twin delivery during cesarean delivery 13,14 .…”

Section: Introductionmentioning

confidence: 99%

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Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide

Anbe

Okawa

Sugawara

et al. 2007

J of Obstet and Gynaecol

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide

Anbe

Okawa

Sugawara

et al. 2007

J of Obstet and Gynaecol

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“…Primers for 18S ribosomal RNA were used as internal positive controls under the same conditions. The steady-state mRNA levels are expressed in arbitrary units as the ratio of iNOS/18S expression (23).…”

Section: Semiquantitative Reverse Transcription-polymerase Chain Reacmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury

Peng

Abdulnour

Sammani

et al. 2005

Am J Respir Crit Care Med

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Rationale: Inducible nitric oxide synthase (iNOS) has been implicated in the development of acute lung injury. Recent studies indicate a role for mechanical stress in iNOS and endothelial NOS (eNOS) regulation. Objectives: This study investigated changes in lung NOS expression and activity in a mouse model of ventilatorinduced lung injury. Methods: C57BL/6J (wild-type [WT]) and iNOSdeficient (iNOS Ϫ/Ϫ ) mice received spontaneous ventilation (control) or mechanical ventilation (MV; VT of 7 and 20 ml/kg) for 2 hours, after which NOS gene expression and activity were determined and pulmonary capillary leakage assessed by the Evans blue albumin assay. Results: iNOS mRNA and protein expression was absent in iNOS Ϫ/Ϫ mice, minimal in WT control mice, but significantly upregulated in response to 2 hours of MV. In contrast, eNOS protein was decreased in WT mice, and nonsignificantly increased in iNOS Ϫ/Ϫ mice, as compared with control animals. iNOS and eNOS activities followed similar patterns in WT and iNOS Ϫ/Ϫ mice. MV caused acute lung injury as suggested by cell infiltration and nitrotyrosine accumulation in the lung, and a significant increase in bronchoalveolar lavage cell count in WT mice, findings that were reduced in iNOS Ϫ/Ϫ mice. Finally, Evans blue albumin accumulation in lungs of WT mice was significant (50 vs. 15% increase in iNOS Ϫ/Ϫ mice compared with control animals) in response to MV and was prevented by treatment of the animals with the iNOS inhibitor aminoguanidine. Conclusion: Taken together, our results indicate that iNOS gene expression and activity are significantly upregulated and contribute to lung edema in ventilator-induced lung injury.Keywords: inducible nitric oxide synthase; lung permeability; mechanical ventilation Nitric oxide (NO) is involved in many physiologic and pathologic conditions, such as blood vessel relaxation, neurotransmission, and host defense. NO also plays a critical role in tissue injury in the context of various inflammatory conditions (1). NO is produced by three isoforms (neuronal, endothelial, and inducible) of NO synthase (NOS). Endothelial NOS (eNOS), which is calcium/calmodulin (Ca 2ϩ /CaM)-dependent and activated by agonists (e.g., acetylcholine), produces a low level of NO output, whereas inducible NOS (iNOS) is independent of Ca 2ϩ /CaM, is transcriptionally regulated by proinflammatory products (e.g., LPS) and cytokines (interleukin 1␤ [IL-1␤], tumor necrosis factor ␣ [TNF-␣], IFN-␥), and results in sustained and elevated (Received in original form November 19, 2004; accepted in final form May 20, 2005) Supported by awards from the National Heart, Lung, and Blood Institute (NIH R01 HL049441 and P50 HL 73994).* These authors contributed equally to the work presented in this article. release of NO (2). Therefore, overproduction of NO, in particular in the setting of superoxide production (3), leads to oxidative stress and tissue injury in conditions such as endotoxin-induced acute lung injury (ALI) (4).ALI is characterized by a severe inflammatory process, pr...

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“…Recently, we demonstrated that the expression of iNOS mRNA in the rat uterus is dependent on implantation, and the gestational increase in iNOS mRNA expression is dependent on the local presence of the conceptus, as well as on circulating factors 22 . Similar to expression of iNOS, cGMP levels were increased during pregnancy and decreased at parturition 17 .…”

Section: Commentmentioning

confidence: 99%

Expression of inducible nitric oxide synthase messenger RNA, but not guanylate cyclase messenger RNA, depends on gestational age in rat myometrium

Okawa

Asano

Takahashi

et al. 2004

Gynecological Endocrinology

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We studied the expression of inducible nitric oxide (NO) synthase (iNOS) and soluble guanylate cyclase (sGC) mRNAs in pregnant rat myometrium. Expression of iNOS and sGC alpha1, beta1 and beta2 mRNA was analyzed in non-pregnant and pregnant (days 10, 14, 17 and 21) Wistar rats by reverse transcription-polymerase chain reaction. Expression of iNOS mRNA increased during pregnancy but decreased on day 21 of gestation. Expression of GC alpha1 mRNA was greater than GC beta1 mRNA at all time points. Expression of uterine GC alpha1 and GC beta1 mRNA did not change significantly during pregnancy and did not differ significantly from non-pregnant levels. The values of sGC beta2 mRNA were below the limit of detection. In conclusion, the expression of iNOS mRNA increased during pregnancy in the myometrium and decreased at term, while the expression of sGC mRNA was not affected by pregnancy. Thus, it is the changes in NO production, rather than changes in its target, that are responsible for uterine quiescence during pregnancy and initiation of labor.

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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

Cited by 12 publications

References 28 publications

Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide

Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide

Inducible Nitric Oxide Synthase Contributes to Ventilator-induced Lung Injury

Expression of inducible nitric oxide synthase messenger RNA, but not guanylate cyclase messenger RNA, depends on gestational age in rat myometrium

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