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Gene Review

NNOS  -  nitric oxide synthase

Ovis aries

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Disease relevance of NNOS


High impact information on NNOS


Chemical compound and disease context of NNOS


Biological context of NNOS

  • We conclude that all three isoforms of NOS are constitutively expressed within the fetal brainstem, and the expression of all three forms is reduced with advancing gestation [15].
  • We speculate that the reduced expression of NOS in this brain region plays a role in the increased fetal baroreflex activity in late gestation [15].
  • Endothelial (e) nitric oxide synthase (NOS) activity modulates pulmonary vascular tone in the normal fetus and decreases pulmonary vascular resistance (PVR) at birth [16].
  • Acylation targets emdothelial nitric-oxide synthase to plasmalemmal caveolae [17].
  • The effects of cell growth induced by serum stimulation were also evaluated, and NOS enzymatic activity was threefold greater in quiescent, serum-deprived cells compared with that in serum-stimulated cells [18].

Anatomical context of NNOS


Associations of NNOS with chemical compounds


Regulatory relationships of NNOS


Other interactions of NNOS


Analytical, diagnostic and therapeutic context of NNOS

  • After at least 14 days, animals were killed, and lungs were harvested for histology, immunostaining, Western blot analysis for eNOS protein content, and biochemical assays of NOS activity [28].
  • We conclude that, despite the absence of pulmonary blood flow and marked lung hypoplasia, eNOS content and NOS activity were not reduced after LPA ligation in the late fetal lung [28].
  • Thus, we investigated the vasoconstrictive effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in sheep, in which a reversible sympathetic block was established by thoracic epidural anesthesia [29].
  • MATERIALS AND METHODS: Longitudinal and transverse sections of the external urethral sphincter from 10 female and 10 male lambs were studied using reduced nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry and nNOS immunocytochemistry [30].
  • OBJECTIVE: To determine whether methylene blue (MB), an inhibitor of soluble guanylate cyclase and nitric oxide synthase, alters lung hemodynamics and fluid filtration after endotoxin in sheep [31].


  1. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Wedgwood, S., McMullan, D.M., Bekker, J.M., Fineman, J.R., Black, S.M. Circ. Res. (2001) [Pubmed]
  2. Effect of ONO1714, a specific inducible nitric oxide synthase inhibitor, on lung lymph filtration and gas exchange during endotoxemia in unanesthetized sheep. Koizumi, T., Ogasawara, H., Yamamato, H., Tsushima, K., Ruan, Z., Jian, M., Fujimoto, K., Kubo, K. Anesthesiology (2004) [Pubmed]
  3. Effect of chronic hypoxemia on the regulation of nitric-oxide synthase in the fetal sheep brain. Aguan, K., Murotsuki, J., Gagnon, R., Thompson, L.P., Weiner, C.P. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  4. Nitric oxide and pregnancy. Sladek, S.M., Magness, R.R., Conrad, K.P. Am. J. Physiol. (1997) [Pubmed]
  5. Nitric oxide synthase inhibition restores hypoxic pulmonary vasoconstriction in sepsis. Fischer, S.R., Deyo, D.J., Bone, H.G., McGuire, R., Traber, L.D., Traber, D.L. Am. J. Respir. Crit. Care Med. (1997) [Pubmed]
  6. Nitric oxide and macrophage function. MacMicking, J., Xie, Q.W., Nathan, C. Annu. Rev. Immunol. (1997) [Pubmed]
  7. Formation of olfactory memories mediated by nitric oxide. Kendrick, K.M., Guevara-Guzman, R., Zorrilla, J., Hinton, M.R., Broad, K.D., Mimmack, M., Ohkura, S. Nature (1997) [Pubmed]
  8. Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors. Kane, D.W., Tesauro, T., Koizumi, T., Gupta, R., Newman, J.H. J. Clin. Invest. (1994) [Pubmed]
  9. Lipocortin 1 mediates the inhibition by dexamethasone of the induction by endotoxin of nitric oxide synthase in the rat. Wu, C.C., Croxtall, J.D., Perretti, M., Bryant, C.E., Thiemermann, C., Flower, R.J., Vane, J.R. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  10. Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Booke, M., Hinder, F., McGuire, R., Traber, L.D., Traber, D.L. Crit. Care Med. (1996) [Pubmed]
  11. Modulation of systemic hemodynamics by exogenous L-arginine in normal and bacteremic sheep. Lorente, J.A., Delgado, M.A., Tejedor, C., Mon, E., Hervás, M., Pascual, T., Fernández-Segoviano, P., Rieppi, G., Soler, A., Ayuso, D., Esteban, A. Crit. Care Med. (1999) [Pubmed]
  12. Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb. Oishi, P., Grobe, A., Benavidez, E., Ovadia, B., Harmon, C., Ross, G.A., Hendricks-Munoz, K., Xu, J., Black, S.M., Fineman, J.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  13. Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep. Guan, J., Bennet, T.L., George, S., Waldvogel, H.J., Faull, R.L., Gluckman, P.D., Keunen, H., Gunn, A.J. Neuroscience (2000) [Pubmed]
  14. Induced cerebral hypothermia reduces post-hypoxic loss of phenotypic striatal neurons in preterm fetal sheep. George, S., Scotter, J., Dean, J.M., Bennet, L., Waldvogel, H.J., Guan, J., Faull, R.L., Gunn, A.J. Exp. Neurol. (2007) [Pubmed]
  15. Expression of nitric oxide synthase isoforms is reduced in late-gestation ovine fetal brainstem. Wood, C.E., Chen, G.F., Keller-Wood, M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) [Pubmed]
  16. Chronic intrauterine pulmonary hypertension impairs endothelial nitric oxide synthase in the ovine fetus. Villamor, E., Le Cras, T.D., Horan, M.P., Halbower, A.C., Tuder, R.M., Abman, S.H. Am. J. Physiol. (1997) [Pubmed]
  17. Acylation targets emdothelial nitric-oxide synthase to plasmalemmal caveolae. Shaul, P.W., Smart, E.J., Robinson, L.J., German, Z., Yuhanna, I.S., Ying, Y., Anderson, R.G., Michel, T. J. Biol. Chem. (1996) [Pubmed]
  18. Cell growth modulates nitric oxide synthase expression in fetal pulmonary artery endothelial cells. Whitney, J.A., German, Z., Sherman, T.S., Yuhanna, I.S., Shaul, P.W. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  19. Effects of pulsatile shear stress on nitric oxide production and endothelial cell nitric oxide synthase expression by ovine fetoplacental artery endothelial cells. Li, Y., Zheng, J., Bird, I.M., Magness, R.R. Biol. Reprod. (2003) [Pubmed]
  20. Estrogen selectively up-regulates eNOS and nNOS in reproductive arteries by transcriptional mechanisms. Rosenfeld, C.R., Chen, C., Roy, T., Liu, X. J. Soc. Gynecol. Investig. (2003) [Pubmed]
  21. Nitric oxide synthase isoform expression in the developing lung epithelium. Sherman, T.S., Chen, Z., Yuhanna, I.S., Lau, K.S., Margraf, L.R., Shaul, P.W. Am. J. Physiol. (1999) [Pubmed]
  22. Prolonged infusions of estradiol dilate the ovine fetal pulmonary circulation. Parker, T.A., Kinsella, J.P., Galan, H.L., Le Cras, T.D., Richter, G.T., Markham, N.E., Abman, S.H. Pediatr. Res. (2000) [Pubmed]
  23. Paracrine role of soluble guanylate cyclase and type III nitric oxide synthase in ovine fetal pulmonary circulation: a double labeling immunohistochemical study. Tzao, C., Nickerson, P.A., Russell, J.A., Noble, B.K., Steinhorn, R.H. Histochem. Cell Biol. (2003) [Pubmed]
  24. Effects of endotoxin exposure on cationic amino acid transporter function in ovine peripheral blood mononuclear cells. Clark, M.F., Reade, M.C., Boyd, C.A., Young, J.D. Exp. Physiol. (2003) [Pubmed]
  25. Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2alpha-induced regression in sheep. Vonnahme, K.A., Redmer, D.A., Borowczyk, E., Bilski, J.J., Luther, J.S., Johnson, M.L., Reynolds, L.P., Grazul-Bilska, A.T. Reproduction (2006) [Pubmed]
  26. Involvement of glutathione as a mechanism of indirect protection against spontaneous ex vivo apoptosis associated with bovine leukemia virus. Sanchez Alcaraz, T., Kerkhofs, P., Reichert, M., Kettmann, R., Willems, L. J. Virol. (2004) [Pubmed]
  27. The premammillary hypothalamic area of the ewe: anatomical characterization of a melatonin target area mediating seasonal reproduction. Sliwowska, J.H., Billings, H.J., Goodman, R.L., Coolen, L.M., Lehman, M.N. Biol. Reprod. (2004) [Pubmed]
  28. Persistent eNOS in lung hypoplasia caused by left pulmonary artery ligation in the ovine fetus. Tajchman, U.W., Tuder, R.M., Horan, M., Parker, T.A., Abman, S.H. Am. J. Physiol. (1997) [Pubmed]
  29. Effects of sympathetic nerve blockade on vasoconstrictive properties of nitric oxide synthase inhibition in sheep. Booke, M., Waurick, R., Van Aken, H., Bone, H.G., Meissner, A., Prien, T., Meyer, J. Cardiovasc. Res. (1997) [Pubmed]
  30. Nitric oxide synthase in the external urethral sphincter of the sheep: immunohistochemical and functional study. González-Soriano, J., Martín-Palacios, S., Rodríguez-Veiga, E., Triguero, D., Costa, G., Garcia-Pascual, A. J. Urol. (2003) [Pubmed]
  31. Methylene blue reduces lung fluid filtration during the early phase of endotoxemia in awake sheep. Evgenov, O.V., Sager, G., Bjertnaes, L.J. Crit. Care Med. (2001) [Pubmed]
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