Nitric oxide synthase activity in the gravid rat uterus decreases a day before the onset of parturition


      OBJECTIVE: Our purpose was to determine the timing, tissue location, and isoform of the uterine nitric oxide synthase activity decrease at term in gravid rat uteri. STUDY DESIGN: Nitric oxide synthase specific activity was assayed in rat uteri 11 through 22 days' gestation by the difference in radiolabeled arginine to citrulline conversion with and without the cofactor reduced nicotinamide adenine dinucleotide phosphate. Nitric oxide synthase isoform was assessed by calcium sensitivity and subcellular location. RESULTS: Rat uterine nitric oxide synthase activity decreased between days 15 and 21 of gestation but did not decrease further at term (day 22), before and after the onset of labor. Decidual nitric oxide synthase activity exceeded the myometrial activity at 15 days' gestation, but then the two were equal at 18 through 22 days' gestation. The nitric oxide synthase activity was calcium insensitive except for half the decidual cytosolic activity on day 15. CONCLUSION: The decrease in pregnant rat uterine nitric oxide synthase activity coincides with the preparation of the uterus for parturition rather than the final activation of labor. (Am J Obstet Gynecol 1996;175:1661-7.)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Challis JRG.
        Characteristics of parturition.
        in: Maternal fetal medicine. Saunders, Philadelphia1994: 482-493
        • Sladek SM
        • Regenstein AC
        • Lykins D
        • Roberts JM.
        Nitric oxide synthase activity in pregnant rabbit uterus decreases on the last day of pregnancy.
        Am J Obstet Gynecol. 1993; 169: 1285-1291
        • Yallampalli C
        • Garfield RE
        • Byam-Smith M.
        Nitric oxide inhibits uterine contractility during pregnancy but not during delivery.
        Endocrinology. 1993; 133: 1899-1902
        • Kumar D
        • Zourlas PA
        • Barnes AC.
        In vivo effect of amyl nitrite on human pregnant uterine contractility.
        Am J Obstet Gynecol. 1965; 91: 1066-1068
        • Nathan C.
        Nitric oxide as a secretory product of mammalian cells.
        FASEB J. 1992; 6: 3051-3064
        • Vince GS
        • Starkey PM
        • Jackson MC
        • Sargent IL
        • Redman CWG.
        Flow cytometric characterisation of cell populations in human pregnancy decidua and isolation of decidual macrophages.
        J Immunol Methods. 1990; 132: 181-189
        • Natuzzi ES
        • Ursell PC
        • Harrison M
        • Busher C
        • Riemer RK.
        Nitric oxide synthase activity in the pregnant uterus decreases at parturition.
        Biochem Biophys Res Commun. 1993; 194: 1-8
        • Weiner CP
        • Knowles RG
        • Nelson SE
        • Stegink LD
        Pregnancy increases guanosine 3’,5’-monophosphate in the myometrium independent of nitric oxide synthesis.
        Endocrinology. 1994; 135: 2473-2478
        • Marletta MA.
        Nitric oxide synthase structure and mechanism.
        J Biol Chem. 1993; 268: 12231-12234
        • Hevel JM
        • White KA
        • Marletta MA.
        Purification of the inducible murine macrophage nitric oxide synthase.
        J Biol Chem. 1991; 266: 22789-22791
        • Luss H
        • DiSilvio M
        • Litton AL
        • Molina y Vedia L
        • Nussler AK
        • Billiar TR.
        Inhibition of nitric oxide synthesis enhances the expression of inducible nitric oxide synthase mRNA and protein in a model of chronic liver inflammation.
        Biochem Biophys Res Commun. 1994; 204: 635-640
        • Robertson CA
        • Green BG
        • Niedzwiecki L
        • Harrison RK
        • Grant SK.
        Effect of nitric oxide synthase substrate analog inhibitors on rat liver arginase.
        Biochem Biophys Res Commun. 1993; 197: 523-528
        • Bhargava S
        • Murugesan K
        • Vij U
        • Farooq A
        Effect of tamoxifen, estradiol 17β on coenzymes NAD, NADPH and the metabolism of estradiol and estrone in rabbit uterus in vivo.
        Indian J Exp Biol. 1993; 31: 940-943
        • Werner-Felmayer G
        • Werner ER
        • Fuchs D
        • Hausen A
        • Reibnegger G
        • Wachter H.
        Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts.
        J Exp Med. 1990; 172: 1599-1607
        • Schmidt HHW
        • Gagne GD
        • Nakane M
        • Pollock JS
        • Miller MF
        • Murad F.
        Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction.
        J Histochem Cytochem. 1992; 40: 1439-1456
        • Tracey WR
        • Nakane M
        • Pollock JS
        • Forstermann U.
        Nitric oxide synthases in neuronal cells, macrophages and endothelium are NADPH diaphorases, but represent only a fraction of total cellular NADPH diaphorase activity.
        Biochem Biophys Res Commun. 1993; 195: 1035-1040
        • Huang J
        • Roby KF
        • Pace JL
        • Russell SW
        • Hunt JS.
        Cellular localization and hormonal regulation of inducible nitric oxide synthase in cycling mouse uterus.
        J Leukoc Biol. 1995; 57: 27-35
        • Yallampali C
        • Izumi H
        • Byam-Smith M
        • Garfield RE
        An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy.
        Am J Obstet Gynecol. 1994; 170: 175-185
        • Tefler JF
        • Lyall F
        • Norman JE
        • Cameron IT.
        Identification of nitric oxide synthase in human uterus.
        Hum Reprod. 1995; 10: 19-23
        • Michel T
        • Li GK
        • Busconi L.
        Phosphorylation and subcellular translocation of endothelial nitric oxide synthase.
        Proc Natl Acad Sci U S A. 1993; 90: 6252-6256
        • Lowenstein CJ
        • Glatt CS
        • Bredt DS
        • Synder SH.
        Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme.
        Proc Natl Acad Sci U S A. 1992; 89: 6711-6715
        • Geller DA
        • Lowenstein CJ
        • Shapiro RA
        • Nussler AK
        • Di Silvio M
        • Wang SC
        • et al.
        Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.
        Proc Natl Acad Sci U S A. 1993; 90: 3491-3495
        • Umans JG
        • Lindheimer MD
        • Barron WM.
        Pressor effect of endothelium-derived relaxing factor inhibition in conscious virgin and gravid rats.
        Am J Physiol. 1990; 259: F293-F296
        • Wei XQ
        • Charles IG
        • Smith A
        • Ure J
        • Feng GJ
        • Huang FP
        • et al.
        Altered immune resonses in mice lacking inducible nitric oxide synthase.
        Nature. 1995; 375: 408-411
        • Conrad KP
        • Joffe GM
        • Kruszyna H
        • Kruszyna R
        • Rochelle LG
        • Smith RP
        • et al.
        Identification of increased nitric oxide biosynthesis during pregnancy in rats.
        FASEB J. 1993; 7: 566-571
        • Stamler JS.
        Redox signaling: nitrosylation and related target interactions of nitric oxide.
        Cell. 1994; 78: 931-936