Nitrik Oksitin İnsan Sağlığındaki Önemi ve Üretimini Arttırıcı Moleküller

Öz

            İnsan vücudunda yaygın olarak bulunan, birçok hastalıkta öneme sahip olan nitrik oksid gaz formundadır. Merkezi sinir sisteminde nöronal ikincil mesajcı görevini yapan, nörotransmiter NO’in, öğrenme ve bellek işlevinde oldukça etkendir. L-arginine gıdalarla alınan bir amino asittir. L-argininden üretilen NO kan dolaşımını kolaylaştırır, endotelya aktivitesinin düzenlenmesinde rol oynar. Diğer bir amino asit L-ciltrulline, L-arginine benzer bir moleküldür ve NO kaynağıdır. Kırmızı et, balık, tavuk, baklagiller, fındık, kavun, C, E vitaminleri içeren bazı doğal gıdalar içinde L-argainine ve L-ciltrulline birçok besinde bulunmaktadır. Bu günlük beslenme için önemlidir. Ayrıca yeterli miktarda alınmaz ise etkisi düzenli olarak görülmemektedir. NO kalp ve damar sistemi, romatizma, felç, alzaimer gibi birçok hastalıkta etken olduğu gibi merkez sinir sistemi, anksiyete, depresyon ve şizofreni gibi psikiyatrik hastalar da nitrat seviyesi ile ilişkilidir. Bu çalışmada, NO’in metabolizmadaki önemi açıklanmıştır. 

Anahtar Kelimeler

• Nitrik Oksit,L-arginine,L-ciltrulline,Hastalıklar,Ruhsal Bozukluklar

Kaynakça

1. [1] Furchgott, R.F. and Zawadski, J.V., (1980). The Obligatory Role of Endothelial Cells in The Relaxation of Arterial Smooth Muscle by Acetylcholine. Nature, 228, 373.
2. [2] Ignarro, L.J., Buga, G.M., Wood, K.S., Byrns, R.E., and Chaudhuri, G., (1987). Endothelium-Derivied Relaxing Factor Produceed and Released from Artery and Vein is Nitric Oxide. Proc Natl Acad Sci USA. 84: 9265-9.
3. [3] Nussler, A.K. and Billiar, T.R., (1993). Inflammation, Immunoregulation and Inducible Nitric Oxide Synthase. J Leukoc Biol (USA). 54(2):171-8.
4. [4] Archer, S.L., (1993). Measurement of Nitric Oxide in Biological Models FASEB J. 7(2):349-60).
5. [5] Kılınç, A., (2003). Nitrik Oksit Biyolojik Fonksiyonları ve Toksik Etkileri. Palme Yayıncılık. 1-59.
6. [6] Moncadia, S., (1999), The Nobel Prize for Nitric Oxide. The Unjust Exclusion pf dr. Salvador Moncada, de berrazueta JR, Rev Esp Cardiol, The Nobel Prize for Nitric Oxide. The unjust exclusion of Dr. Salvador Moncada, Rev Esp Cardiol. 52(4):221-6.
7. [7] Bansal, V., and Ochoa, J.B., (2003). Arginine Avalability, Arginine and The Immune Response, Curr Opin Clin Nutr Metp Care. 6:223-228.
8. [8] Pamuk, F., (2000). Biyokimya; Gazi Kitapevi. Sy.274.

9. [9] Furchgotta, R., Ignora L., and Murad F., (1998). Nobel Prize Awarded to Scientists for Nitric Oxide Discoveries. 98(22):2365-2366.
10. [10] Cooke, J.P., (1997). Dearangement of The Nitric Oxide Synthase Pathway, L-Arginine, And Cardiovascular Diseases. Jul 15, 96(2):667-75.
11. [11] Blum, A. and Cannon, R.O., (2001). L-arginine for the Prevention and Treatment of Coronary Artery Disease. Coronary Artery Disease. 12:535-9.
12. [12] Takita, T., Ikeda, J., Sekiguchi, Y., Demachi., J., Li, S.L., and Shirato, K., (1998). Nitric Oxide Modulates Symphathic Control of Left Ventricular Contraction in Vivo in The Dog. J Autonomic Nervous System. 71, 69-74.
13. [13] Benjamin, N., Datton, J.A.E, and Riter, J.M., (1991). Human Vascular Smooth Muscle Cells Inhibit Platelet Aggregation When Incubated with Glyceryl Trinitrate: Evidence for Generation of Nitric Oxide. Br. J. Pharmacol. 102:847-850.
14. [14] Marin, J., and Rodriguez-Martinez M.A., (1997). Role of Vascular Nitric Oxide in Physiological and Pathological Conditions. Pharmacol. Ther. 75, 111-134.
15. [15] Li, H. and Förstermann, U., (2000). Nitric Oxide in The Pathogenesis of Vascular Diseases. J Pathol. 190, 244-254.
16. [16] Joannides, R., Richard, R., Haefeli, W.E., Linder, L., Lüscher, T.F., and Thuillez, C., (1995). Role of Basal and Stimulated Release of Nitric Oxide in the Regulation of Radial Artery Caliber in Humans. Hypertension. 26:327-31.
17. [17] Sessa, W.C., Prithchard, K., Seyedi, N., Wang, J., and Hintze T.H., (1994). Chronic Excercise in Dogs Increases Coronary Vascular Nitric Oxide Production and Endothelial Cell Nitric Oxide Synthase Gene Expression. Circ Res 74:349-53.
18. [18] Hishikawa, K. and Lüscher, T.F., (1997). Pulsatile Strech Situmulates Süper Oxide Production in Human Aortic Endothelial Cells. Circulation. 96:3610-6.
19. [19] Lahera, V., Salom, M.G., Miranda, G.F., Moncada, S., and Romero, J.C., (1991). Effects of NG-nitro-L-arginine Methyl Ester on Renal Function and Blood Pressure. Am J Physiol. 261:1033-7.
20. [20] Braman, R.S. and Hendrix, S.A., (1989). Nanogram Nitrite and Nitrate Determination in Environmental and Biological Materials by Vanadium (III) Reduction whit Chemiluminescense Detection. Anal Chem. (24):2715-8.
21. [21] Stuehr, D.J. and Marletta, M.A., (1985). Mammalian Nitrate Biosynthesis: Mouse Macrophages Produce Nitrite and Nitrate in Response to Escherichiacoli Lipopolysaccharide. Proc Natl Acad Sci USA. 82: 7738-42.
22. [22] Hibbs, J.B.J, Taintor, R.R., and Vavrin, Z., (1987). Macrophage Cytotoxicity: Role for L-arginine Deiminase and Imino Nitrogen Oxidation to Nitrite. Science. 235:473-76.
23. [23] Chinje, E.C. and Stratford, I.J., (1997). Role of Nitric Oxide in Growth of Solid Tumours: a Balancing act. Essays Biochem. 32:61-72.
24. [24] Huerta, S., Chilka, S., and Bonovida, B., (2008). Nitric Oxide Donors: Novel Cancer Therapeutics Review, Int.j. Oncol. 33:909-927.
25. [25] Bonavida, B., Khineche, S., Huerta-Yepez, S., and Garban, H., (2006). Therapeutic Potential of Nitric Oxide in Cancer, Drug Resist. Updat. 9(3):157–173.
26. [26] Stefanovic, Racic, M., Stadier, J., and Evans, C.H., (1993). Nitric Oxide and Arthrits. Arthritis Rheum. 36:1036-44.
27. [27] Stichlenoth, D.O., Wallenhoupt, J., Anderson, D., et al., (1995). Elavated Serum Nitrate Concentrations in Active Spondylo Arthropathles. Br J Rheumatol. 34:616-9.
28. [28] Fletcher, D.S., Widmer, W.R., and Luel, S., (1998). Therapeutic Administration of A Selective Inhibitor of Nitric Oxide Synthase Does not Amellorate The Chronic Inflamation and Tissue Damage Associated whit Adjuvant-İnduced Arthritis In Rats. J Pharmacol Exp Ther. 284; 714-21.
29. [29] Garthwaite, J., Charles, S.L., and Chess-Williams, R., (1988). Endothelium-Derived Relaxing Factor Release on Acitivation of NMDA Receptors Suggest Role as Intercellular Messenger in The Brain. Nature.336:385-388.
30. [30] Hirsch, D.P., Holloway, R.H., Tygat, G.N.J., and Boeckxstaens, E.E., (1998). Involvement of Nitric Oxide in Human Transient Lower Esophageal Spinccter Relaxation and Esophageal Primaly Peristalsis. Gastroenterology. 115(6):1374-1380.
31. [31] Javelle, N., Berod, A., Renaud, B., and Lambas-Senas, L., (2002). NO Synthase Inhibitors Attenuate Locus Coeruleus Catecholamine Metabolism and Behavior Induced by Morphine Withdrawal. NeuroReport, 13:725-728.
32. [32] Dawson, T.M, Gonzalez-Zulueta, M., Kusel, J., and Dawson V.L., (1998). Nitric Oxide: Diverse Actions in the Central and Peripheral Nervous Systems. The Neuroscientist, 4:96-112.
33. [33] Moncada, S. and Higss, A., (1993). The L-arginine-Nitric Oxide Pathway. N Engl J Med. 329:2002-2012.
34. [34] Dawson, T.M., Bredt, D.S., Fotuhi, M., Hwang, P.M., and Snyder, S.H., (1991). Nitric Oxide Synthase and Neuronal Nadph Diaphorase are ıdentical in Brain and Peripheral Tissues. Proc Natl Acad Sci USA. 88:7797-7801.
35. [35] Lancaster, J.R., (1997). A Tutorial on The Diffusibility and Reactivity of Free Nitric Oxide. Nitric Oxide. 1:18-30.
36. [36] Sadock, B.J. and Sadock, V.A., (2000). Comprehensive Textbook of Psychiatry, 7th edn. Philadelphia: Lippincott Williams &Wilkins. 159-165.
37. [37] Kopf, S.R., Benton, R.S., Kalfin, R., Giovannini, M.G., and Pepeu, G., (2001). NO Synthesis Inhibition Decreases Cortical ACh Release and Impairs Retention of Aconditioned Response. Brain Res.894:141-144.
38. [38] Wood, P.L., Emet, M.R., Rao, T.S., and et al., (1990). Nitric Oxide Mediates N-Methyl-D-Aspartate, Quisqualate and Kinate Dependent İncreases İn Cerebellar Cyclic Gmp İn Vivo. J Neurochem. 55:346-348.
39. [39] Prast, H. and Philippu, A., (2001). Nitric Oxide as Modulator of Neuronal Function. Prog Neurobiol, 64:51-68.
40. [40] Rollof, E.V. and Platt, B., (1999). Biochemical Dysfunction and Memory Loss; the Case of Alzaimer’s Dementin. Cell, Mol.Life Sci, 55:601-616.
41. [41] Posada, A. and Clarke, P.G.H., (1999). Role of Nitric Oxide in a Fast Retrograde Signal During Devopment. Dev. Brain. Res. 114:37-42.
42. [42] Smith, M.A., Rottcamp, C.A., Numora, A., Raina, A.K., and Perry, G., (2000). Oxidative Stres in Alzaimer’s Disease, Biochim. Biophys. Acta, 1502:139-144.
43. [43] Lüscher, T.F. and Barton. M., (1997): Biology of the Endothelium. Clin Cardiol. 20 (Suppl II), 3-10.
44. [44] Lopez, A.D., Mather, C.D., Ezzati, M., and Jamison, D.T., (2006). Global and Regional of Disease and Risk Factors, Sysatematic Analiysis of Population Health Data. The Lancet. 367:1747-1757.
45. [45] Vincent, J.L., Zhang, H., Szabo, C., and Preiser, J.C., (2000). Effects of Nitric Oxide in Septic Shock. Am. J. Resir. Crit. Care Med. 161:1781-1785.
46. [46] Kishimito, J., Tsuchiya, T., Emson, P.C., and Nakayama, N., (1996). Mobilization-induced Stres Activates Neuronal Nitric Oxide Synthase (nNOS) mRNA and Protein in Hypothalamic-pituitary-adrenal Axis in Rats. Brain Res, 720:159-171.
47. [47] Echeverry, M.B. and Guimräres, F.S., (2004). Del Bel EA. Acute and Delayed Festraint Stress-Induced Changes in Nitric Oxide Producing Neurons in Limbic Regions. Neuroscience, 125:981-993.
48. [48] Meloni, D., Gambarana, C., and De Montis, (1993). Dizocilpine Antagonizes the Effect of Chronic Imipramine on Learning Helplessness in Rats. Pharmacol Biochem Behav. 46:423-426.
49. [49] Yıldız, F., Erden, B.F., Ulak, G., Utkan, T., and Gacar, N., (2000). Antidepressant like effect of 7- Nitroindazole in the Forced Swimming Test in Rats. Psychopharmacology, 65:199-202.
50. [50] Heiberg, I.L., Wegener, G., and Rosenberg, R., (2002). Reduction of cgmp Nitric Oxide has Antidepressant Like Effects in the Forced Swimming Test in R ats. Behav Brain Res. 134:479-484.
51. [51] Garthwaite, J., Charles, S.L., and Chess-Williams, R., (1988). Endothelium-Derived Relaxing Factor Release on Acitivation of NMDA Receptors Suggest Role as Intercellular Messenger in The Brain. Nature. 336:385-388.
52. [52] Baba, H., Suzuki, T., Arai, H., and Emson, P.C., (2004). Expression of nNOS and Soluble Guanylate Cyclase in Schizophrenic Brain. NeuroReport, 15(4):677-680.
53. [53] Calapa, G., Mazzaglia, G., Sautebin, L., et al., (1996). Inhibition Nitric Oxide Formation Reduces Voluntary Ethanol Consumption in Rat. Psychopharmacology. 125:398-401.
54. [54] Vincent, S.R. and Kimura H., (1992). Histochemical Mapping of Nitric Oxide Synthase in The Rat Brain. Neuroscience. 46:755-784.
55. [55] Dunn, R.W., Corbett, R., and Fielding, S., (1989). Effects of 5-HT 1A Receptor Antagonists in The Social İnteraction Test and The Elevated Plus Maze. Eur J Pharmacol. 169:1-10.
56. [56] Zhang, J. and Snyder, S.H., (1995). Nitirc Oxide in Nervous System. Annu Rev Pharmacol Toxicol. 35:213-233.
57. [57] Yanik, M., Vural, H., Koctigit, A., et al., (2003). Is the Aarginine-nitric Oxide Pathway Involved in the Pathogenesis of Schizphrenia? Neuropsychobiology. 47(2):61-65.
58. [58] Das, I., Khan, N.S., Puri, B.K., and et al., (1995). Elevated Plasma Calcium Mobilization and Nitric Oxide Synthase Activity May Reflect Abnormalities in Schizophrenic Brain. Biochem Biophys Res Commun. 212:375-380.
59. [59] Lue, W.M., Su, M.T., Lin, W.B., and Tao, P.L., (1999). The Role of Nitiric Oxide in The Development of Morphine Tolerance in Rat Hippocampal Slices. Eur J Pharmacol. 383:129-135.
60. [60] Bredt, D.S. and Snyder, S.H., (1992). Nitric Oxide, a Novel Neuronal Messenger. Neuron. 8:3-11.
61. [61] Colas, D., Gharib, A., Bezin, L., and et al., (2006). Regional Age-Related Changes in Nöronal Nitric Oxide Synthase (nNOS), Messenger RNA Levels and Activity in SAMP8 Brain. BMC Neuroscience. 7:81-87.