Periferik Vasküler Hastalığın Tedavisinde İloprost’tun Nitrik Oksit, Asimetrik Dimetilarjinin ve Serotonin’e Etkisi

Yıl 2020, Cilt: 3 Sayı: 3, 106 - 110, 31.12.2020

Sefa Şenol

https://doi.org/10.33713/egetbd.832603

Öz

Özet
Amaç: Bu çalışmada periferik arter hastalarında iloprost kullanılımının dolaşımdaki asetil dimetil arjinin (ADMA), Serotonin ve Nitrik Oksit (NO) gibi endotelyal fonksiyonlarda görev alan parametreler üzerindeki etkinliğinin araştırılması hedeflenmiştir.
Materyal Metod : Çalışmaya Fontaine III-IV hastalığı tanısıyla takip edilip medikal tedavi kararı verilen 30 olgu (19’u erkek, 11’i kadın, yaş aralığı ise 60.7 ± 13.7 ) alındı. Hastalara iloprost infüzyonu ön kol venlerinden 0.5-1.5 ng/kg/dk dozunda 16 saatlik intravenöz infüzyon şeklinde başlandı ve 7 gün verildi. Tedavi öncesi ve sonrası ( 8. günde) ADMA, Serotonin ve NO sonuçları için kan alındı. Total nitrit (nitrit + nitrat) konsantrasyonu modifiye kadmiyum redüksiyon metodu ile, ADMA ve serotonin düzeyleri High Performance Liquid Chromotography (HPLC) yöntemiyle ölçüldü.
Bulgular: İloprost tedavisi öncesi ve sonrası ADMA değeri tedavi sonrası düşmüş olup bu istatistiksel olarak anlamlı iken (p=0.001), Serotonin (p=0.82) ve NO (P= 0.16) değerlerindeki degişiklikler istatistiksel olarak anlamsız bulunmuştur.
Sonuç: Periferal arteryel hastalıklarda iloprost tedavisi sonrası endotelyal disfonksiyon göstergesi olarak kabul edilen ADMA’nın azaldığını ve periferik arteryel hastalarında kullanılan tedavinin değerlendirilmesinde dikkate alınabilinecek bir parametre olabilir .

Anahtar Kelimeler

İloprost, Nitrik Oksit, ADMA, Serotonin

Teşekkür

Bu makale Fırat Üniversitesi Tıp Fakültesi Kalp Damar Cerrahisi için hazırlanmış olan ”Periferik Vasküler Hastalığın Tedavisinde İloprost’tun Nitrik Oksit,Asimetrik Dimetilarjinin ve Serotonin’e Etkisi" isimli tıpta uzmanlık tezinden üretilmiştir. (Tez numarası: 299008). Çalışmanın bilimsel yönüne katkılarından ve eğitim desteğinden dolayı Prof. Dr. Oktay BURMA'ya teşekkür ederim.

The Effect of Iloprost on Nitric Oxide, Asymmetric Dimethyl Arginine and Serotonin in the Treatment of Peripheral Vascular Disease

Öz

Aim: In this study, it is aimed to investigate the efficacy of iloprost use in peripheral artery disease patients on the parameters involved in endothelial functions such as circulating acetyl dimethyl arginine (ADMA), serotonin and nitric oxide (NO).
Patients and Methods: 30 patients (19 male, 11 female, age interval 60.7 ± 13.7) who were followed-up with the diagnosis of Fontaine III-IV disease and decided to receive a medical treatment were included in the study. Iloprost infusion was initiated as a 16-hour intravenous infusion at the dose of 0.5-1.5 ng / kg / min from the forearm veins and was given for 7 days. Blood was taken for ADMA, Serotonin and NO results before and after the treatment (8th day). Total nitrite (nitrite + nitrate) concentration was measured by the modified cadmium reduction method, ADMA and serotonin levels were measured by High Performance Liquid Chromotography (HPLC) method.
Results: ADMA value before and after the iloprost treatment was decreased after the treatment and while this was statistically significant (p=0.001), the changes in serotonin (p=0.82) and NO (P= 0.16) values were found statistically insignificant.
Conclisions: Peripheral arterial disease may be a parameter that can be taken into account in the evaluation of treatment for peripheral arterial disease and ADMA, which is considered to be an endothelial dysfunction indicator after iloprost treatment.

Anahtar Kelimeler

Iloprost, Nitric Oxide, ADMA, Serotonin

Kaynakça

• 1. Akgül E, Erdolu B, Vural AH, Yumun G, Özyazıcıoglu AF. An evaluation of the effect of biodegradable stents on restenosis in the treatment of peripheral arterial lesions. Turk Gogus Kalp Dama. 2017;25(2):203-208.
• 2. Hansson GK, Nilsson J. Pathogenesis of atherosclerosis. Crawford MH, DiMarco JP (eds). Cardiology. 1st edition, Mosby International Ltd. England, 2003.
• 3. Gülcü A, Sezer C, Taşbaş BA. Adjuvan Treatment In Avascular Necrosıs Of Femoral Head. Acta Med. Alanya 2017;1(3): 55-57
• 4. Mazzone A, Vezzoli M, Ottini E, Montagna M, Mazzucchelli L, Dal Canton A. A new method of iloprost administration without a peristaltic pump. Curr Ther Res 2000;61:452–9.
• 5. Debey S, Kirchrath L, Schrör K, Meyer-Kirchrath J. Iloprost down-regulates the expression of the growth regulatory gene Cur61 in human vascular smooth muscle cells. Eur J Pharmacol 2003;474:161–4.
• 6. Landmesser U, Drexler H. The clinical significance of endothelial dysfunction. Curr Opin Cardiol 2005;20:547-51.
• 7. Brunini T, Moss M, Siqueira M, Meirelles L, Rozentul A, Mann G, et al. Inhibition of l-arginine transport in platelets by asymmetric dimethylarginine and N-monomethyl-l-arginine: effects of arterial hypertension. Clin Exp Pharmacol Physiol. 2004;31(10):738-40. doi: 10.1111/j.1440-1681.2004.04067.x. PMID: 15554917.
• 8. Hliser D. Asymmetric dimethylarginine (ADMA): the silent transition from an uremic toxin’ to a global cardiovascular risk molecule. European Journal of Clinical Investigation 2005; 35: 71-79.
• 9. Vallance P, Leiper J. Cardiovascular Biology of the Asymmetric Dimethylarginine: Dimethylarginine Dimethylaminohydrolase Pathway. Arterioscler Thromb Vasc Biol. 2004; 24: 1023-1030.
• 10. Teerlink T. Measurement of asymmetric dimethylarginine in plazma: methodological considerations and clinical revelence. Clin Chem Lab Med.2005;43:1130-B.
• 11. Lentz S R, Rodinov R N, Dayal S. Hyperhomocysteinemia,endothelial dysfunction, and cardiovascular risk: the potential role of ADMA. Atherosclerosis Supplements 2003; 4:61-65.
• 12. Lessiani G, Vazzana N, Cuccurullo C, Di Michele D, Laurora G, Sgrò G, et al. Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost. Thromb Haemost 2011;105(2):321-8.
• 13. Teerlink T. Measurement of asymmetric dimethylarginine in plazma: methodological considerations and clinical revelence. Clin Chem Lab Med.2005;43:1130-B.
• 14. Belch JJ. Metabolic, endocrine and hemodynamic risk factors in the patientwith Peripheral arterial disease. Diabetes Obes. Metab. 2002;4 Suppl 2:S7-13.
• 15. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-67. doi: 10.1016/j.jvs.2006.12.037.
• 16. Gardner AW, Afaq A. Management of lower extremity peripheral arterial disease. J Cardiopulm Rehabil Prev 2008;28:349-57.
• 17. Blardi P, de Lalla A, Pieragalli D, De Franco V, Meini S, Ceccatelli L, et al. Effect of iloprost on plasma asymmetric dimethylarginine and plasma and platelet serotonin in patients with peripheral arterial occlusive disease. Prostaglandins Other Lipid Mediat. 2006;80(3-4):175-82. doi: 10.1016/j.prostaglandins.2006.06.005. PMID: 16939882.
• 18. Tran CT, Leiper J M., Vallance P. The DDAH/ ADMA/NOS pathway. Atherosclerosis Supplements 2003; 4:33–40.
• 19. Hara K, Hirowatari Y, Takahashi H. The ratio of plasma to whole-blood serotonin may be a novel marker of atherosclerotic cardiovascular disease. J Lab Clin Med 2004; 144: 31-377.
• 20. Norel X, Sugimoto Y, Ozen G, Abdelazeem H, Amgoud Y, Bouhadoun A, et al. International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E2 Receptors (EP1-4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions. Pharmacol Rev. 2020;72(4):910-968. doi: 10.1124/pr.120.019331. PMID: 32962984; PMCID: PMC7509579.
• 21. Wei Ni, Stephanie W Watts. 5-Hydroxytryptamıne In The Cardıovascular System: Focus On The Serotonın Transporter (Sert). Clinical And Experimental Pharmacology And Physiology 2006; 33:575–83.
• 22. Schoenichen C, Bode C, Duerschmied D. Role of platelet serotonin in innate immune cell recruitment. Front Biosci (Landmark Ed). 2019;24:514-526. PMID: 30468670.
• 23. Vanhoutte PM, Chapter 22 - Serotonin: a forgotten signal from the blood, Editor(s): Müller CP, Cunningham KA, Handbook of Behavioral Neuroscience, Elsevier, 2030;(31):393-409, ISSN 1569-7339, ISBN 9780444641250, https://doi.org/10.1016/B978-0-444-64125-0.00022-0.
• 24. Kim JG, Leem YE, Kwon I, Kang JS, Bae YM, Cho H. Estrogen modulates serotonin effects on vasoconstriction through Src inhibition. Exp Mol Med. 2018;50(12):1-9. doi: 10.1038/s12276-018-0193-z. PMID: 30559345; PMCID: PMC6297153.
• 25. Vong LB, Bui TQ, Tomita T, Sakamoto H, Hiramatsu Y, Nagasaki Y. Novel angiogenesis therapeutics by redox injectable hydrogel - Regulation of local nitric oxide generation for effective cardiovascular therapy. Biomaterials. 2018;167:143-152. doi: 10.1016/j.biomaterials.2018.03.023.
• 26. Senol S, Senol A. Investigation of Asymmetric and Symmetric Dimethylarginine Levels after Iloprost Treatment in Patients with Buerger's Disease. Eur J Vasc Endovasc Surg. 2017;53(3):439-442.
• 27. Jacobi J, Sydow K, von Degenfeld G, Zhang Y, Dayoub H, Wang B, et al. Overexpression of dimethylarginine dimethylaminohydrolase reduces tissue asymmetric dimethylarginine levels and enhances angiogenesis. Circulation 2005;111:1431-8.
• 28. Mukai M, Komori K, Oka T. Mechanism and Management of Cancer Chemotherapy-Induced Atherosclerosis. J Atheroscler Thromb. 2018;25(10):994-1002. doi: 10.5551/jat.RV17027. Epub 2018 Sep 14. PMID: 30224607; PMCID: PMC6193189.
• 29. Tapia-Vieyra JV, Delgado-Coello B, Mas-Oliva J. Atherosclerosis and Cancer; A Resemblance with Far-reaching Implications. Arch Med Res. 2017;48(1):12-26. doi: 10.1016/j.arcmed.2017.03.005. PMID: 28577865.