Akut Submaksimal Egzersizin Trombosit Aktivasyonu ve Endotel Üzerine Etkisi

Abstract

Trombositlerin koroner hastalığın oluşumundaki önemli rolleri egzersizin trombosit fonksiyonları üzerine etkisinin yoğun olarak araştırılmasına yol açmıştır. Literatürde farklı süre ve şiddette, akut ve kronik egzersize trombosit yanıtlarına dair çok sayıda çalışma vardır. Katekolaminlerin artışı, α adrenerjik reseptör aktivasyonu, trombosit sayısında, PGI2/TxA2 dengesinde, trombositlerin NO ve PGI2’e duyarlılığındaki değişiklikler gibi farklı mekanizmalar trombositlerin egzersize verdiği yanıtın altında yatan mekanizmalar olarak öne sürülmektedir. Sunulan çalışmada, orta şiddette akut egzersizin trombosit aktivasyonuna etkileri ve bu etkide endotelin rolünün araştırılması amaçlandı. Bu amaçla, trombosit aktivasyon göstergesi olarak trombosit glikoprotein IIbIIIa (GPIIb/IIIa) düzeyleri, endotel fonksiyonunu değerlendirmek amacı ile plazma NO düzeyi ve trombositlerde NO yanıtına aracılık eden cGMP düzeyleri değerlendirildi. Çalışmaya 19 sedanter, sağlıklı erkek gönüllü katıldı. Gönüllülere 15 dakikalık %60 VO2max şiddetinde bisiklet egzersizi uygulandı. Egzersiz öncesi ve hemen sonrası alınan kan örneklerinden trombosit GPIIb/IIIa, plazma NO ve trombosit cGMP düzeyleri ELISA yöntemi ile ölçüldü. GPIIb/IIIa düzeyleri egzersiz sonrası istatistiksel olarak anlamlı derecede (p=0.024) düşük bulundu. Egzersiz öncesi ve sonrası plazma NO düzeyleri ile trombosit cGMP düzeylerinde istatistiksel olarak anlamlı bir değişim gözlenmedi. Plazma NO ve trombosit cGMP düzeyleri ile trombosit GPIIb/IIIA düzeyleri arasında korelasyon saptanmadı. Trombosit GPIIb/IIIa seviyelerinde düşüş literatürdeki şiddetli egzersiz ile trombosit fonksiyon artışı, orta şiddette egzersiz ile trombosit fonksiyonlarında değişme olmaması ya da trombositlerin baskılanması bulguları ile uyumludur. Plazma NO düzeyi ve trombosit cGMP düzeyinde değişiklik olmaması inhibisyonun farklı mekanizmalarla olabileceğini düşündürmüştür.

Keywords

• Akut egzersiz,Submaksimal egzersiz,Trombosit,GPIIbIIIa,Endotel,NO

The Effect of Submaximal Acute Exercise on Platelet Activation and Endothelium

Abstract

The key role of platelets in the pathogenesis of coronary heart disease prompted considerable interest on the effect of exercise on platelets. There are several studies shown the effects of various intensities and durations of acute or chronic exercise on platelets. The exact mechanisms and the regulatory pathways concerned in the effect of exercise on platelet function are not completely understood. Increase in plasma levels of cathecolamines, change in the performance of 􀁄􀀐adrenergic reseptors, increase in platelet count, PGI2/TxA2 imbalance, impaired sensity of platelets to prostacyclin (PGI2) and nitric oxide (NO) have been suggested as probable mechanisms. In the present study we aimed to examine the effect of submaximal exercise on platelet activation and the role of endothel. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) as a marker of platelet activation and NO as a marker of endothel activation, and cGMP which mediates the intracellular effects of NO in platelets were evaluated. Nineteen, sedentary male volunteers (aged 18-25) participated the study. Volunteers performed 15 minutes of cycling exercise at a workload that increased their heart rate to 60% of the maximal. Platelet GPIIb/IIIa, plasma NO and platelet cGMP were measured by enzyme-linked immunassay (ELISA) before and immediately after the exercise. Platelet GPIIb/IIIa significantly decreased after the exercise protocol (p=0.024). No significant difference was found between plasma NO and cGMP. There was no correlation between platelet GPIIb/IIIa and both plasma NO and platelet cGMP levels. The data was confirmed by the literature. The submaximal exercise performed in the present study was inhibited by the platelet activation since NO levels did not increase. We found no clear-cut relationship between platelet GPIIb/IIIa and plasma NO. It was thought that different mechanisms were involved in the inhibition of platelets.

Keywords

• Acute,Submaximal,Exercise,Platelets,Endothel

References

1. Aird W.C. (2005). Vasodilation and Vasoconstriction, Endothelial Cells in Health and Disease. Taylor & Francis Group.: 199-211
2. Aker A. (2010). Epitel Doku ve Endotel. Erişim: http//. tipedu.cumhuriyet.edu.tr tipedu.cumhuriyet.edu.tr/ Donem2/I.Komite(DokuKomitesi)/Biyokimya. Erişim tarihi: 15.04.
3. Astrand P.O. , Rodahl K. (1986). Evalution physical work capacity on the basis of tests. Textbook of Work Physiology : 3. Edition, McGraw-Hill Book Company, Printed in the U.S.A., s.: 354-387.
4. Astrand P.O., Rhyming I.A. (1954). Nomogramfor calculation aerobic capacity (physical fitness) from pulse rate during submaxsimal work. J Appl Physol. : 7:218.
5. Aurigemma C, Fattorossi, A, Sestito A, Sgueglia, G. A, Farnetti, S, Buzzonetti, A, Infusino, F, Landolfi R, Scambia, G, Crea, F, Lanza, G. A. (2007). Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise Thrombosis Research: 120: 901–909.
6. Brass, L.F. (2000). The Molecular Basis for Platelet Activation. In Heamatology Basic Principles and Practice. Eds Hoffman, R., Benz, E.J., Shattil, S.J., Furie, B., Cohen, H.J., Sılberstein, L.E., McGlave, 3rd Edition ,Churchil Livingstone, USA, s.:1753-1769.
7. Beam W.C, Adams G.M. (2013). Egzersiz Fziyolojisi Laboratuvar El Kitabı (Özer M.K Çeviren). Nobel Akademik Yayıncılık. Ankara. 8. Brooks
8. G.A., Fahey T.D. (1985). Cardiovasculer

9. dynamics during exercise. Exercise Physiology :Human
10. Bioenergetics and Its applications, MacMillian Published
11. Company, Printed in the U.S.A., s.: 313 – 41.
12. Brooks G.A. , Fahey T.D. (1985). The how of ventilation. Exercise Physiology :Human Bioenergetics and Its applications, MacMillian Published Company, Printed in the U.S.A., s.: 239 – 70.
13. Davies M., Thomas A.C., Knapman P.A., Hangartner J.R. (1986). Intramyocardial platelet aggregation in patients with unstable angine suffering sudden ischemic cardiac death. Circulation: 73: 418 – 27.
14. Davies P. F. (1995). Flow mediated endothelial mechanotransduction. Physiol Rev: 75: 519 – 560
15. De Graaf JC, Banga JD, Moncada S, Palmer RMJ, de Groot PG, Sixma JJ. (1992). Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation, 85:2284-2290.
16. De Meirelles LR, Mendes-Ribeiro AC, Mendes MA, da Silva MN, Ellory JC, Mann GE, Brunini TM.Scand J. (2009). Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway. Med Sci Sports, 19(1);67.
17. Di Massimo C, Scrapelli P, Tozzi-Ciancarelli M.G. (2004). Possible Involment Of Oxidative Stress in Exercise Mediated Platelet Activation. Clinical Hemorheology And Microcirculation: 30; 313-316
18. Drygas W.K. (1988). Changes in blood platelet function, coagulation and fibrinolytic activity in response to moderate, exhaustive and prolonged exercise. Int J Sports Med: 8: 67 – 72
19. Dzau VJ. (2001). Tissue Angiotensin and Pathobiology of Vascular Disease. A Unifying Hypothesis. Hypertension: 37; 1047-1052.
20. El-Sayed. (2002). Exercise and training effects on platelets in health and disease. Platelets 13, 261– 266.
21. Ersöz G. (1997). Trombosit Aktivasyonu. Ankara Üniversitesi Tıp Fakültesi Mecmuası. Cilt 50. 3:163-172.
22. Ersöz G. (2002). Trombosit ve Nötrofiller Arasında Fonksiyonel Etkileşimin İn Vitro Koşullarda İncelenmesi. T.F.B.D. 28. Ulusal kongresi.
23. Ganong W.F. (2012). Blood as a Circulatory Fluid & the Dynamics of Blood & Lymph Flow  ; Platelets, Ganong’s Review of Medical Physiology. 24th edition, Lange: 555- 586.
24. Gencer E. (2009). Yenidoğanlarda Trombosit Fonksiyonları ve Endotel İlişkisi. Yayımlanmamış Uzmanlık Tezi. Ankara Üniv. Sağlık Bilimleri Enstitüsü.
25. Holme P.A, Orvim U, Hamers M.J, Solum N.O, Brosstad F.R, Barstad R.M, Sakariassen K.S. (1997). Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis. Arterioscler Thromb Vasc Biol 17: 646–53.
26. Jones CJH, DeFily DV, Patterson JL, Chilian WM. (1993). Endothelium dependent relaxation competes with D1- and D2-adrenergic constriction in the canine epicardial coronary microcirculation. 87:1264-1274. Circulation,
27. Jones N.L. (1988). Approaches to clinical exercise testing. Clinical exercise testing, 3. Edition, W.B. Saunders Company, Made in the U.S.A., s.: 123-34.
28. Jones N.L. (1988). Physiology of exercise. Clinical exercise testing, 3. Edition, W.B. Saunders Company, Made in the U.S.A., s.: 13-73.
29. Kleinbongard P, Schulz R, Rassaf T, Lauer T, Dejam A, Jax T, Kumara I, Gharini P, Kabanova S, Ozüyaman B, Schnürch HG, Gödecke A, Weber AA, Robenek M, Robenek H, Bloch W, Rösen P, Kelm M. (2006). Red blood cells express a functional endothelial nitric oxide synthase. Blood. Apr 1; 107(7):2943-2951.
30. Kuhn, K. and Eble, J. (1994). Trends Cell Biol. 4:256.
31. Legge B.J., Banister E.W. (1986). The Astrand- Rhyming nomogram revisited. J Appl Physiol: 61: 1203- 1209.
32. Lindemann S, Klingel B, Fisch A, Meyer J, Darius H. (1999). Increased Platelet Sensivity Toward Platelet Inhibitors During Physical Exercise in Patients With Coronery Artery Disease. Thrombosis Research: 93:51- 59.
33. Meirelles L. R., Mendes-Ribeiro A. C., Mendes M. A. P., da Silva M. N. S. B, John J.C., Ellory Clive, Mann G.E., Brunini T.M.C. (2009). Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway. Scand J Med Sci Sports: 19: 67–74.
34. Nims R.W., Darbyshire J.F. Saavedra J.E. et al. (1995). Colorimetric methods fort he determination of nitric oxide concentration in neutral aqueous solutions. Methods 7, 48-54.
35. Oates JA, Fitzgerald GA, Branch RA, Jackson EK, Knapp HR, Roberts LJ. (1988). Clinical implications of prostaglandin and thromboxane A2 formation N Engl J Med, 319:689-698.
36. Plow E. F, Ginsberg M.H. (2000). The Molecular Basis for Platelet Function. In Heamatology Basic Principles and Practice., 3rd Edition ,Churchil Livingstone, USA, 1741-1752.
37. Rowel L.B. (1990). Exercise physiology. Princaples of physiology, Edited by Berne R.M., Levy M.N. , The C.V. Mosby Company , Chapter 46 , s.: 1-29
38. Sakita, S., Kishi, Y., Numano, F. (1997). Acute vigorous exercise attenuartes sensivity of platelets to nitric oxide. Thromb Res 87 (5): 461 – 471.
39. Saltin B. (1989). Oxygen Transport during Exercise: Role of the cardiovasculer system. Biological effects of physical activity, Edited by William R.S. , Wallace A.G. , Human kinetic publishers, Printed in the U.S.A. , s.: 3-24.
40. Siess W. (1989). Molecular mechanisms of Platelet Activation. Physiol Rew 69(1):58.
41. Torun E., Bayram F. (2004). Endokrin Bir Organ Olarak Endotel ve Endotelin Hiptrtensiyondaki Rolü. Erciyes Tıp Dergisi (Erciyes Medical Journal) 26 (3): 126-131.
42. Tozzi M. G, Ciancarelli M., P.C, Di M. (2002). Influence of acute exercise on human platelet responsiveness: possible involment of exercise – induced oxidative stress. European Journal of Applied Physiology, Volume 86, 3: 266-272.
43. Vischer U.M, Wollheim C.B. (1997). Epinephrine induces von Willebrand factor release from cultured endothelial cells: involvement of cyclic AMP-dependent signalling in exocytosis. Thromb Haemost: 77:1182–88.
44. Wang J., Jen, C.J., Kug, H., Lin, L., Hsiue, T&Chen, H. (1994). Different effects of strenuous exercise on platelet function in men. Circulation 90:2877-2885.
45. Wang J.S, Cheng L-J. (1999). The effect of strenuous acute exercise on 2-adrenergic agonist-potentiated platelet activation. Arterioscler Thromb Vasc Biol 19:1559–1565.
46. Wang J.S. (2004). Intense exercise increases shear-induced platelet aggregation in men through enhancement of von Willbrand factor binding, glycoproteinIIb/IIIa activation, and P-selectin expression on platelets Eur J Appl Physiol: 91: 741–47.
47. Weber A.A, Heım H.K, Schumacher M, Schror K, Hohlfeld T. (2007). Effects of selective cyclooxygenase isoform inhibition on systemic prostacyclin synthesis and on platelet function at rest and after exercise in healthy volunteers. Platelets, August; 18(5): 379–385.
48. Williams W, Beutler E, Erslew A, Lichtman M. (1991). Platelet morphology and function. In Heamatology, 4. Edition, McGrav-Hill Book Company, U.S.A. s.:1172.
49. Wu X, Brüne B, Von Appen F, Ullrich V. (1992). Efflux of cyclic GMP from activated human platelets. Mol Pharmacol. 43: 564-568.
50. Zucher D, Franklin D. (2000). Megakaryocyte and
51. Platelet Structure. In Heamatology Basic Principles and Practice. USA, 1730-1740.