Nitric oxide—Important messenger in human body

Martina Antosova, Jana Plevkova, Anna Strapkova, Tomas Buday

Department of Pathological Physiology Jessenius Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Department of Pharmacology Jessenius Faculty of Medicine, Comenius University, Bratislava, Slovakia.

DOI: 10.4236/ojmip.2012.23014                

Abstract

General idea of this comprehensive review is to summarize information about the role of nitric oxide in the human body—cardiovascular, respiratory, urgenital, gut, NO and immune system, however, NO signaling has a role also in musculoskeletal system, even in bones. NO in the past had been recognized as a molecule relevant to air pollution. In 1980 Furchgott and Zawadzki identified new messenger molecule within the endothelial cells with vasodilating potential and they named it endothelium derived relaxing factor (EDRF). Seven years later the role of NO as a relaxing factor was definitely proven. The fact of gas, being produced by cells, crossing membranes of neighboring cells and having a character of signal brought a brand new insight to the signaling physiology. The breakthrough in the NO history was in 1992, when it was assigned as “molecule of the year”. Role of NO was defined mainly in the cardiovascular sys-tem, but as the research expanded, the ultimate func-tion, and mechanism of action, dual effect of NO had been identified in all systems of human body. NO in low concentrations considerably regulates the physiological functions, but in high concentration may contribute to the pathogenetic process. Knowledge the physiology of NO signaling cascades could have clinical application, mainly considering therapeutic poten-tial of NO donors, or antagonists of NO-synthases. This molecule has undoubtedly huge future potential.

Keywords

Nitric Oxide; Physiology; Signaling

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Anggard, E. (1994) Nitric oxide: Mediator, murderer, and medicine. Lancet, 343, 1199-1206. doi:10.1016/S0140-6736(94)92405-8
[2]	Carvajal, J.A., Germain, A.M., Huidobro-Toro, J.P. and Weiner, C.P. (2000) Molecular mechanism of cGMPmediated smooth muscle relaxation. Journal of Cellular Physiology, 184, 409-420. doi:10.1002/1097-4652(200009)184:3<409::AID-JCP16>3.0.CO;2-K
[3]	Francis, S.H., Busch, J.L., Corbin, J.D. and Sibley, D. (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacological Reviews, 62, 525-563. doi:10.1124/pr.110.002907
[4]	Jerca, L., Jerca, O., Mancas, G., Constantinescu, I. and Lupusoru, R. (2002) Mechanism of action and biochemical effects of nitric oxide (NO). The Journal of Preventive Medicine, 10, 35-45.
[5]	Garcia-Calvo, M., Knaus, H.G., McManus, O.B., Giangiacam, K.M., Kaczorowski, G.J. and Garcia, M.L. (1994) Purification and reconstitution of the high-conductance, calcium activated potassium channel from tracheal smooth muscle. Journal of Biological Chemistry, 269, 676-682.
[6]	Knott, A.B. and Bossy-Wetzel, E. (2009) Nitric Oxide in Health and Disease of the Nervous System. Antioxidants & Redox Signaling, 11, 541-554.
[7]	Calabrese, V., Mancuso, C., Calvani, C., Rizzarelli, E., Butterfield, D. and Stella, A.M. (2007) Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nature Reviews Neuroscience, 10, 766-775. doi:10.1038/nrn2214
[8]	Bult, H., Boeckxstaens, G.E., Pelckmans, P.A., Jordaens, F.H., Van Maercke, Y.M. and Herman, A.G. (1990) Nitric oxide as an inhibitory non-adrenergic noncholinergic neurotransmitter. Nature, 345, 346-347. doi:10.1038/345346a0
[9]	Hollenberg, N.K. (2006) Organ systems dependent on nitric oxide and the potential for nitric oxide-targeted therapies in related diseases. The Journal of Clinical Hypertension, 12, 63-73. doi:10.1111/j.1524-6175.2006.06042.x
[10]	Ignarro, L.J. (2002) Nitric oxide as a unique signaling molecule in the vascular system: A historical overview. Journal of Physiology and Pharmacology, 53, 503-514.
[11]	Bae, E.H., Kim, I.J., Ma, S.K., Lee, J.U. and Kim, S.W. (2011) Altered regulation of renal nitric oxide and atrial natriuretic peptide systems in lipopolysaccharide-induced kidney injury. Korean Journal of Physiology & Pharmacology, 15, 273-277. doi:10.4196/kjpp.2011.15.5.273
[12]	Strijdom, H., Chamane, N. and Lochner, A. (2009) Nitric oxide in the cardiovascular system: A simple molecule with complex actions. Cardiovascular Journal of Africa, 20, 303-310.
[13]	Lv, L., Jiang, S.S., Xu, J., Gong, J.B. and Cheng, Y. (2012) Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: The role of endothelial nitric oxide synthase. Clinical and Experimental Pharmacology and Physiology, 39, 20-27. doi:10.1111/j.1440-1681.2011.05628.x
[14]	Dweik, R.A. (2001) The promise and reality of nitric oxide in the diagnosis and treatment of lung disease. Cleveland Clinic Journal of Medicine, 68, 486-490. doi:10.3949/ccjm.68.6.486
[15]	Careau, E., Sirois, J. and Bissonnette, E.Y. (2002) Characterization of lung hyperresponsiveness, inflammation, and alveolar macrophage mediator production in allergy resistant and susceptible rats. American Journal of Respiratory Cell and Molecular Biology, 26, 579-586.
[16]	Aiko, O. (2002) Pulmonary nitric oxide in preterm and term infants with respiratory failure. Act Universitatis Ouluensis Medica, Oulu University Press, Oulu, 74.
[17]	Adler, K.B., Fischer, B.M., Li, H., Chloe, N.H. and Wright, D.T. (1995) Hyper secretion of cumin is response to inflammatory mediators by guinea pig tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide syntheses. American Journal of Respiratory Cell and Molecular Biology, 13, 526-530. doi:10.1152/physrev.00034.2003
[18]	Ricciardolo, F.L.M., Sterk, P.J., Gaston, B. and Folkerts, G. (2004) Nitric oxide in health and disease of the respiratory system. Physiological Research, 84, 731-765.
[19]	Dijkstra, G., van Goor, H., Jansen, P.L. and Moshage, H. (2004) Targeting nitric oxide in the gastrointestinal tract. Current Opinion in Investigational Drugs, 5, 529-536.
[20]	Russo, A., Fraser, R., Adachi, K., Horowitz, M. and Boeckxstaens, G. (1999) Evidence that nitric oxide mechanisms regulate small intestinal motility in humans. Gut, 44, 72-76. doi:10.1136/gut.44.1.72
[21]	Stark, M.E. and Szurszewski, J.H. (1992) Role of nitric oxide in gastrointestinal and hepatic function and disease. Gastroenterology, 103, 1928-1949.
[22]	Stanek, A., Gadowska-Cicha, A., Gawron, K., Wielkoszynski, T., Adamek, B., Gieslar, G., Wiczkowski, A. and Sieron, A. (2008) Role of nitric oxide in physiology and phatology of the gastrointestional tract. Mini-Reviews in Medicinal Chemistry, 8, 1549-1560. doi:10.2174/138955708786786462
[23]	Sharma, S.P. (2004) Nitric oxide and the kidney. Indian Journal of Nephrology, 14, 77-84.
[24]	Baylis, C.H. (2008) Nitric oxide deficiency in chronic kidney disease. American Journal of Physiology—Renal Physiology, 294, F1-F9. doi:10.1152/ajprenal.00424.2007
[25]	Sugino, N., Takiguci, S., Ono, M., Tamura, H., Shimamura, K., Nakamura, Y., Tsuruta, R., Sadamitsu, D., Ueda, T., Maekawa, T. and Kato, H. (1996) Nitric oxide concentration in the follicular fluid and apoptosis of granulosa cells in human follicles. Human Reproduction, 11, 2484-2487. doi:10.1093/oxfordjournals.humrep.a019144
[26]	Magness, R.R., Shaw, C.E., Pherretton, T.M., Zheng, J. and Bird, I.M. (1997) Endothelial vasodilator production by uterine and systemic arteries. II. Pregnancy effects on NO synthase expression. American Journal of Physiology, 272, H1730-H1740.
[27]	Momohara, Y., Sakamoto, S., Obayashi, S., Aso, T., Goto, M. and Azuma, H. (2004) Roles of endogenous nitric oxide synthase inhibitors and endothelin-1 for regulating myometrial contractions during gestation in the rat. Molecular Human Reproduction, 10, 505-512. doi:10.1093/molehr/gah072
[28]	Rosselli, M., Keller, P.J. and Dubey, R.K. (1998) Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Human Reproduction Update, 4, 324. doi:10.1093/humupd/4.1.3
[29]	Davidoff, M.S., Middendorff, R., Mayer, B., de Vente, J., Koesling, D. and Holstein, A.F. (1997) Nitric oxide/ cGMP pathway components in the Leydig cells of the human testis. Cell Tissue, 287, 161-170. doi:10.1007/s004410050742
[30]	Bogdan, C. (2001) Nitric oxide and the immune response. Nature Immunology, 2, 907-916. doi:10.1038/ni1001-907
[31]	Karpuzoglu, E. and Ahmed, S.A. (2006) Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: Implications for immunity, autoimmune diseases, and apoptosis. Nitric Oxide, 15, 177186. doi:10.1016/j.niox.2006.03.009