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Gene Review

Nos3  -  nitric oxide synthase 3, endothelial cell

Mus musculus

Synonyms: 2310065A03Rik, Constitutive NOS, EC-NOS, Ecnos, Endothelial NOS, ...
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Disease relevance of Nos3


Psychiatry related information on Nos3


High impact information on Nos3


Chemical compound and disease context of Nos3


Biological context of Nos3


Anatomical context of Nos3


Associations of Nos3 with chemical compounds

  • In addition, benfotiamine prevented the vascular accumulation of advanced glycation end products and the induction of pro-apoptotic caspase-3, while restoring proper expression of Nos3 and Akt in ischaemic muscles [22].
  • Nitric oxide (NO) produced by the constitutive NO synthase (cNOS) in neurons has been implicated in mediating excitotoxic neuronal death [23].
  • Enalapril treatment abolishes the deleterious effects of eNOS deficiency on BP, atherosclerosis, and kidney dysfunction in nnee mice [24].
  • BMDMØs from eNOS KO animals exhibited reduced nuclear factor-kappaB activity, iNOS expression, and NO production after exposure to lipopolysaccharide (LPS) as compared with cells derived from wild-type mice [21].
  • The aim of this study was to investigate the regulation of endothelial nitric oxide synthase (eNOS) activity by acute and chronic elevated glucose [25].
  • These data demonstrate a novel role of Ang II in diabetic uncoupling of eNOS and that Ang II-targeted therapy improves endothelial function via the novel mechanism of recoupling eNOS [26].

Physical interactions of Nos3

  • In addition, the molecular chaperone Hsp90 interacts with eNOS and positively regulates eNOS activity [27].

Enzymatic interactions of Nos3


Regulatory relationships of Nos3


Other interactions of Nos3

  • VEGF superfusion significantly increased permeability in both WT and iNOS(-/-) mice but not in eNOS(-/-) mice [19].
  • These data indicate that NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and that the eNOS isoform may play a dominant role relative to nNOS [34].
  • Intriguingly, similar levels of arterial hypertension are accompanied by marked cardiac hypertrophy in GC-A-/-, but not in eNOS-/-, mice, suggesting that changes in local pathways regulating cardiac growth accelerate cardiac hypertrophy in the former and protect the heart of the latter [2].
  • CONCLUSIONS: The overexpression of TGF-beta1 and eNOS may represent mechanisms in iNOS-KO mice to compensate for their loss of functional iNOS, resulting in incisional wound healing equivalent to controls [35].
  • In eNOS knockout animals, tPA again significantly increased infarct size after transient focal ischemia [30].

Analytical, diagnostic and therapeutic context of Nos3


  1. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Aicher, A., Heeschen, C., Mildner-Rihm, C., Urbich, C., Ihling, C., Technau-Ihling, K., Zeiher, A.M., Dimmeler, S. Nat. Med. (2003) [Pubmed]
  2. Local atrial natriuretic peptide signaling prevents hypertensive cardiac hypertrophy in endothelial nitric-oxide synthase-deficient mice. Bubikat, A., De Windt, L.J., Zetsche, B., Fabritz, L., Sickler, H., Eckardt, D., Gödecke, A., Baba, H.A., Kuhn, M. J. Biol. Chem. (2005) [Pubmed]
  3. Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a pro-inflammatory role for eNOS-derived no in vivo. Connelly, L., Madhani, M., Hobbs, A.J. J. Biol. Chem. (2005) [Pubmed]
  4. autoregulatory role of endothelium-derived nitric oxide (NO) on Lipopolysaccharide-induced vascular inducible NO synthase expression and function. Vo, P.A., Lad, B., Tomlinson, J.A., Francis, S., Ahluwalia, A. J. Biol. Chem. (2005) [Pubmed]
  5. Phosphorylated endothelial nitric oxide synthase mediates vascular endothelial growth factor-induced penile erection. Musicki, B., Palese, M.A., Crone, J.K., Burnett, A.L. Biol. Reprod. (2004) [Pubmed]
  6. Superior water maze performance and increase in fear-related behavior in the endothelial nitric oxide synthase-deficient mouse together with monoamine changes in cerebellum and ventral striatum. Frisch, C., Dere, E., Silva, M.A., Godecke, A., Schrader, J., Huston, J.P. J. Neurosci. (2000) [Pubmed]
  7. Voluntary physical activity alterations in endothelial nitric oxide synthase knockout mice. Momken, I., Lechêne, P., Ventura-Clapier, R., Veksler, V. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  8. Mild hypoxia impairs alveolarization in the endothelial nitric oxide synthase-deficient mouse. Balasubramaniam, V., Tang, J.R., Maxey, A., Plopper, C.G., Abman, S.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  9. A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension. Liu, S., Premont, R.T., Kontos, C.D., Zhu, S., Rockey, D.C. Nat. Med. (2005) [Pubmed]
  10. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Simoncini, T., Hafezi-Moghadam, A., Brazil, D.P., Ley, K., Chin, W.W., Liao, J.K. Nature (2000) [Pubmed]
  11. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Huang, P.L., Huang, Z., Mashimo, H., Bloch, K.D., Moskowitz, M.A., Bevan, J.A., Fishman, M.C. Nature (1995) [Pubmed]
  12. Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood-brain barrier breakdown. Winkler, F., Koedel, U., Kastenbauer, S., Pfister, H.W. J. Infect. Dis. (2001) [Pubmed]
  13. Nitric oxide in obstructive uropathy: role of endothelial nitric oxide synthase. Chang, B., Mathew, R., Palmer, L.S., Valderrama, E., Trachtman, H. J. Urol. (2002) [Pubmed]
  14. Ca(2+) loading and adrenergic stimulation reveal male/female differences in susceptibility to ischemia-reperfusion injury. Cross, H.R., Murphy, E., Steenbergen, C. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  15. Uterine artery remodeling and reproductive performance are impaired in endothelial nitric oxide synthase-deficient mice. van der Heijden, O.W., Essers, Y.P., Fazzi, G., Peeters, L.L., De Mey, J.G., van Eys, G.J. Biol. Reprod. (2005) [Pubmed]
  16. Endothelial-derived nitric oxide and angiotensinogen: blood pressure and metabolism during mouse pregnancy. Hefler, L.A., Tempfer, C.B., Moreno, R.M., O'Brien, W.E., Gregg, A.R. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  17. Inducible and endothelial nitric oxide synthase: genetic background affects ovulation in mice. Hefler, L.A., Gregg, A.R. Fertil. Steril. (2002) [Pubmed]
  18. The gene encoding endothelial nitric oxide synthase, Nos3, maps to rat chromosome 4. Hübner, N., Kreutz, R., Rubattu, S., Lee, Y.A., Ganten, D., Allen, P.D., Lindpaintner, K. Mamm. Genome (1995) [Pubmed]
  19. Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability. Fukumura, D., Gohongi, T., Kadambi, A., Izumi, Y., Ang, J., Yun, C.O., Buerk, D.G., Huang, P.L., Jain, R.K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  20. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. Das, A., Xi, L., Kukreja, R.C. J. Biol. Chem. (2005) [Pubmed]
  21. Macrophage endothelial nitric-oxide synthase autoregulates cellular activation and pro-inflammatory protein expression. Connelly, L., Jacobs, A.T., Palacios-Callender, M., Moncada, S., Hobbs, A.J. J. Biol. Chem. (2003) [Pubmed]
  22. Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Gadau, S., Emanueli, C., Van Linthout, S., Graiani, G., Todaro, M., Meloni, M., Campesi, I., Invernici, G., Spillmann, F., Ward, K., Madeddu, P. Diabetologia (2006) [Pubmed]
  23. Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Hewett, S.J., Csernansky, C.A., Choi, D.W. Neuron (1994) [Pubmed]
  24. Enhanced atherosclerosis and kidney dysfunction in eNOS(-/-)Apoe(-/-) mice are ameliorated by enalapril treatment. Knowles, J.W., Reddick, R.L., Jennette, J.C., Shesely, E.G., Smithies, O., Maeda, N. J. Clin. Invest. (2000) [Pubmed]
  25. Hyperglycaemia-induced superoxide production decreases eNOS expression via AP-1 activation in aortic endothelial cells. Srinivasan, S., Hatley, M.E., Bolick, D.T., Palmer, L.A., Edelstein, D., Brownlee, M., Hedrick, C.C. Diabetologia (2004) [Pubmed]
  26. Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Oak, J.H., Cai, H. Diabetes (2007) [Pubmed]
  27. Chaperone-dependent regulation of endothelial nitric-oxide synthase intracellular trafficking by the co-chaperone/ubiquitin ligase CHIP. Jiang, J., Cyr, D., Babbitt, R.W., Sessa, W.C., Patterson, C. J. Biol. Chem. (2003) [Pubmed]
  28. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. Luo, Z., Fujio, Y., Kureishi, Y., Rudic, R.D., Daumerie, G., Fulton, D., Sessa, W.C., Walsh, K. J. Clin. Invest. (2000) [Pubmed]
  29. Endothelial nitric oxide synthase protects aortic allografts from the development of transplant arteriosclerosis. Lee, P.C., Wang, Z.L., Qian, S., Watkins, S.C., Lizonova, A., Kovesdi, I., Tzeng, E., Simmons, R.L., Billiar, T.R., Shears, L.L. Transplantation (2000) [Pubmed]
  30. Aggravation of focal cerebral ischemia by tissue plasminogen activator is reversed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor but does not depend on endothelial NO synthase. Kilic, E., Kilic, U., Matter, C.M., Lüscher, T.F., Bassetti, C.L., Hermann, D.M. Stroke (2005) [Pubmed]
  31. Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS. Ding, H., Hashem, M., Triggle, C. Eur. J. Pharmacol. (2007) [Pubmed]
  32. Effects of rapamycin on the arterial inflammatory response in atherosclerotic plaques in Apo-E knockout mice. Naoum, J.J., Woodside, K.J., Zhang, S., Rychahou, P.G., Hunter, G.C. Transplant. Proc. (2005) [Pubmed]
  33. Modulation of mouse cardiac function in vivo by eNOS and ANP. Gyurko, R., Kuhlencordt, P., Fishman, M.C., Huang, P.L. Am. J. Physiol. Heart Circ. Physiol. (2000) [Pubmed]
  34. Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Shankar, R.R., Wu, Y., Shen, H.Q., Zhu, J.S., Baron, A.D. Diabetes (2000) [Pubmed]
  35. Characterization of incisional wound healing in inducible nitric oxide synthase knockout mice. Most, D., Efron, D.T., Shi, H.P., Tantry, U.S., Barbul, A. Surgery (2002) [Pubmed]
  36. VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells. Feliers, D., Chen, X., Akis, N., Choudhury, G.G., Madaio, M., Kasinath, B.S. Kidney Int. (2005) [Pubmed]
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