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Effects of melatonin on the tissue factor activities of kidney, heart and brain in experimental renovascular hypertension

Year 2012, Volume: 2 Issue: 2, 78 - 83, 31.01.2014

Abstract

Objective: The aim of the present study was to investigate the effect of melatonin on tissue factor activities (TFa) of kidney, heart and brain in an angiotensin II-dependent renovascular hypertension (RVH) in rats.
Methods: RHV was induced in Wistar albino rats by placing renal artery clip (two-kidney, one-clip; 2K1C). Starting on the operation day (RHV-Mel-1) and 3 weeks after the operation (RHV-Mel-2), the rats received melatonin (10 mg/kg/day) while the control group received 1 mL/kg/day saline with 1% alcohol for the following 6 weeks. Indirect blood pressure (BP) measurement was made by the tail-cuff method. At the end of the 9th week, after BP recordings, kidney, heart and brain tissues were excised and stored at -200C until the analysis of TFa. TFa of tissues were determined according to Quick’s one stage method and results are expressed as seconds.
Results: 2K1C caused increase in BP and TFa of the kidney significantly but did not change TFa of heart and brain compared with the control group. In RVH-Mel-1 group, TFa of kidney decreased compared with the RVH group. TFa of kidney increased in RVH-Mel-2 group compared with the control. On the other hand, the TFa of heart increased in both melatonin-treated RVH groups compared with the control group.
Conclusion: Increased TFa of kidney in RVH group might promote renal artery stenosis and thrombosis development. On the other hand, increased TFa of heart in melatonin treated groups might provide additional hemostatic protections to this vital organ in order to prevent from excessive bleeding.

Key words: Renovascular hypertension, melatonin, tissue factor, kidney, heart, brain, rat

References

  • Connolly JO, Woolfson RG. Renovascular hypertension: diagnosis and management. BJU Int. 2005;96: 5, 715-720.
  • Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87: 840-849.
  • Nishimura H, Tsuji H, Masuda H, Kasahara T, Yoshizumi M, Sugano T, Kimura S, Kawano H, Kunieda Y, Yano S, Nakagawa K, Kitamura H, Nakahara Y, Sawada S, Nakagawa M. The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells. Thromb Haemost. 1999;82: 1516- 1521.
  • Nemerson Y. Tissue factor and hemostasis. Blood. 1988;71: 1-8.
  • Yarat A, Tunali T, Pisiriciler R, Akyuz S, Ipbuker A, Emekli N. Salivary thromboplastic activity in diabetics and healthy controls. Clin Oral Invest. 2004;8(1): 36-39.
  • Emekli-Alturfan E, Kasikci E, Yarat A.Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption. Diabetes Metab Res Rev. 2007;23(8): 653-658.
  • Emekli-Alturfan E, Kasikci E, Yarat A. Peanuts improve blood glutathione, HDL-cholesterol level and change tissue factor activity in rats fed a high-cholesterol diet. Eur J Nutr. 2007;46(8): 476-82.
  • Emekli-Alturfan E, Kasikci E, Alturfan AA, Pisiriciler R, Yarat A. Effect of sample storage on stability of salivary glutathione, lipid peroxidation levels, and tissue factor activity. J Clin Lab Anal. 2009;23(2): 93-98.
  • Emekli-Alturfan E, Basar I, Malali E, Elemek E, Oktay S, Ayan F, Emekli N, Noyan U. Plasma tissue factor levels and salivary tissue factor activities of periodontitis patients with and without cardiovascular disease. Pathophysiol Haemost Thromb. 2010;37(2-4): 77-81.
  • Emekli-Alturfan E, Kasikci E, Yarat A. Effects of oleic acid on the tissue factor activity, blood lipids, antioxidant and oxidant parameters of streptozotocin induced diabetic rats fed a high-cholesterol diet. Med Chem Res. 2010;19(8): 1011-1024.
  • Tremoli E, Camera M, Toschi V, Colli S. Tissue factor in atherosclerosis. Atherosclerosis. 1999;144: 273-83.
  • Morrissey JH. Tissue factor and factor VII initiation of coagulation. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, editors. Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 89-102.
  • Patterson C, Stouffer GA, Madamanchi N, Runge MS. New tricks for old dogs: non-thrombotic effects of thrombin in vessel wall biology. Circ Res. 2001;88: 987-97.
  • Larsson PT, Schwieler JH, Wallen NH. Platelet activation during angiotensin II infusion in healthy volunteers. Blood Coagul Fibrinolysis. 2000;11: 61-9.
  • Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12: 151-180.
  • Faillace MP, Cutrera R, Keller-Sarmento MI, Rosenstein RE. Evidence for local synthesis of melatonin in golden hamster retina. Neuroreport 1995;6: 2093-2095.
  • Bubenik GA. Gastrointestinal melatonin: localization, function and clinical relevance. Dig Dis Sci. 2002;47: 2336-2348.
  • Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni GJM. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000;28: 193-202.
  • Carrillo-Vico A, Calvo JR, Abreu P, Lardone PJ, Garcia-Morino S, Reiter RJ, Guerrero JM. Evidence of melatonin synthesis in human lymphocytes and its physiological significance: possible role as intracrine, autocrine and/or paracrine substance. FASEB J. 2004;18: 537-539.
  • Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Oktani-Kandro R, Hara M, Suzuki T, Reiter RJ. Identification of melatonin in plants: its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995;35: 627-634.
  • Seweynek E. Melatonin and the cardiovascular system. Neuro Endocrinol Lett. 2002;Suppl 1: 79-83.
  • Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999;83: 1417-1419.
  • Reiter RJ, Tan DX, Pilar TM, Flores LJ, Czarnaocki. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim Pol. 2007;54: 1-9.
  • Pang CS, Xi SC, Brown GM, Pang SF, Shiu SY. 2[125I] Iodomelatonin binding and interaction with beta-adrenergic signaling in chick heart/coronary artery physiology. J Pineal Res. 2002;32: 243-252.
  • Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP. MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther. 2002;302: 1295-1302.
  • Tunali T, Sener G, Yarat A, Emekli N. Melatonin reduces oxidative damage to skin and normalizes blood coagulation in a rat model of thermal injury. Life Sci. 2005;28;76(11): 1259-65.
  • Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine. 2005;27: 189-200.
  • Erşahin M, Sehirli O, Toklu HZ, Süleymanoglu S, Emekli-Alturfan E, Yarat A, Tatlidede E, Yeğen BC, Sener G. Melatonin improves cardiovascular function and ameliorates renal, cardiac and cerebral damage in rats with renovascular hypertension. J Pineal Res. 2009;47(1): 97-106.
  • Navar IG, Harrison-Bernard IM, Nishiyama A, Kobori H. Regulation of intrarenal angiotensin II in hypertension. Hypertension. 2002;39: 316- 322.
  • Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on Experimental Hypertension I. The production of persistent elevation of the systolic blood pressure by means of renal ischemia. J Exper Med. 1934;59: 347-379.
  • Ingram GIC & Hills M. Reference method for the one stage prothrombin time test on human blood. Thromb Haemostas. 1976;36: 237-238.
  • Textor SC, Wilcox CS. Renal artery stenosis: a common, treatable cause of renal failure? Annu Rev Med. 2001;52: 421-442.
  • Magrini F, Reggiani P, Roberts N, Meazza R, Ciulla M, Zanchetti A. Effects of angiotensin and angiotensin blockade on coronary circulation and coronary reserve. Am J Med. 1988;84: 55-60.
  • Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin-II mediated cardiovascular and renal diseases. Pharmacol Rev. 2000;52: 11-34.
  • Minuz P, Patrignani P, Gaino S, Degan M, Menapace L, Tommasoli R, Seta F, Capone ML, Tacconelli S, Palatresi S, Bencini C, Del Vecchio C, Mansueto G, Arosio E, Santonastaso CL, Lechi A, Morganti A, Patrono C. Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease. Circulation. 2002;106: 2800- 2805.
  • Muller DN, Mervaala EMA, Schmidt F, Park JK, Dechend R, Genersch E, Breu V, Löffler BM, Ganten D, Schneider W, Haller H, Luft FC. Effect of bosentan on NF-κB, inflammation, and tissue factor in angiotensin II–induced end-organ damage. Hypertension. 2000;36: 282-290.
  • Ushigome H, Yoshimura N, Sano H, Nakamura K, Oka T. Expression of tissue factor in renal ischemic-reperfusion injury of the rat. Transplant Proc.1998;30: 3764-3765.
  • Wendt T, Zhang YM, Bierhaus A, Kriegsmann J, Deng Y, Waldherr R, Teske T, Luther T, Fünfstück R, Nawroth PP. Tissue factor expression in an animal model of hydronephrosis. Nephrol Dial Transplant. 1995;10: 1820-1828.
  • Maki S, Miyauchi T, Sakai S, Kobayashi T, Maeda S, Takata Y, Sugiyama F, Fukamizu A, Murakami K, Goto K, Sugishita Y. Endothelin-1 expression in hearts of transgenic hypertensive mice. J Cardiovasc Pharmacol. 1998;31: S412-S416.
  • Moreau P, d’Uscio LV, Shaw S, Takase H, Barton M, Luscher TF. Angiotensin II increases tissue endothelin and induces vascular hypertrophy: reversal by ET(A)-receptor antagonist. Circulation. 1997;96: 1593-1597.
  • Lockyer JM, Colladay JS, Alperin-Lea WL, Hammond T, Buda AJ. Inhibition of nuclear factor-κB–mediated adhesion molecule expression in human endothelial cells. Circ Res.1998;82: 314-320.
  • Ferro D, Saliola M, Meroni PL, Valesini G, Caroselli C, Praticò D, Fitzgerald GA, Shoenfeld Y, Violi F. Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment. J Thromb Haemost. 2003; 1(3): 523-531.
  • Ferro D, Basili S, Pratico` D, Iuliano L, FitzGerald GA, Violi F. Vitamin E reduces monocyte tissue factor expression in cirrhotic patients. Blood. 1999; 93: 2945-2950.

Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri

Year 2012, Volume: 2 Issue: 2, 78 - 83, 31.01.2014

Abstract

Amaç: Çalışmamızın amacı anjiotensin II bağımlı renovasküler hipertansiyon (RHV) oluşturulmuş sıçanların böbrek, kalp ve beyin dokularının doku faktörü aktivitesi (TFa) üzerine melatoninin etkilerini incelemektir.
Yöntem: RHV Wistar albino sıçanlarda renal arter klips (iki böbrek, bir klips, 2K1C) yerleştirerek oluşturulmuş, kontrol grubuna ise klips yerleştirilmemiştir. Operasyon gününde (RHV-Mel-1) veya operasyondan 3 hafta sonra başlayacak şekilde (RHV-Mel-2) sıçanlara 6 hafta boyunca melatonin (10 mg/kg/gün), kontrol grubuna ise 1 mL/kg/gün salin ile %1 alkol verilmiştir. İndirekt kan basıncı (BP) ölçümü “tail-cuff” metodu ile yapılmıştır. 9. haftanın sonunda BP ölçümleri yapılmıştır. Böbrek, kalp ve beyin dokuları çıkartılarak TFa ölçümlerine kadar -200C’de saklanmıştır. Dokuların TF aktiviteleri “Quick’s one stage” metoduna göre yapıldı ve sonuçlar saniye olarak verildi.
Bulgular: Oluşturulan 2K1C modeli BP’de ve böbrek TFa’da kontrolle karşılaştırıldığında anlamlı artışa neden oldu; ancak, kalp ve beyin TFa’yı etkilemedi. RVH-Mel-1 grubunda, böbrek TFa değeri, RHV grubuyla karşılaştırıldığında azaldı. Böbrek TFa değerlerinin RVH-Mel-2 grubunda kontrol grubuna göre artmış olduğu bulundu. Ancak kalp TFa değerleri kontrol grubuyla karşılaştırıldığında melatonin ile tedavi edilen her iki RHV grubunda arttı.
Sonuç: RHV grubunda artmış böbrek TFa renal arter stenozu ve tromboz gelişimine neden olabilir. Melatonin ile tedavi edilen gruplarda artmış kalp TFa değerleri ise bu hayati organı aşırı kanamadan koruyacak ilave bir hemostatik koruma sağlayabilir.

Anahtar Kelimeler : Renovasküler hipertansiyon, melatonin, doku faktörü, böbrek, kalp, beyin, sıçan

References

  • Connolly JO, Woolfson RG. Renovascular hypertension: diagnosis and management. BJU Int. 2005;96: 5, 715-720.
  • Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87: 840-849.
  • Nishimura H, Tsuji H, Masuda H, Kasahara T, Yoshizumi M, Sugano T, Kimura S, Kawano H, Kunieda Y, Yano S, Nakagawa K, Kitamura H, Nakahara Y, Sawada S, Nakagawa M. The effects of angiotensin metabolites on the regulation of coagulation and fibrinolysis in cultured rat aortic endothelial cells. Thromb Haemost. 1999;82: 1516- 1521.
  • Nemerson Y. Tissue factor and hemostasis. Blood. 1988;71: 1-8.
  • Yarat A, Tunali T, Pisiriciler R, Akyuz S, Ipbuker A, Emekli N. Salivary thromboplastic activity in diabetics and healthy controls. Clin Oral Invest. 2004;8(1): 36-39.
  • Emekli-Alturfan E, Kasikci E, Yarat A.Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption. Diabetes Metab Res Rev. 2007;23(8): 653-658.
  • Emekli-Alturfan E, Kasikci E, Yarat A. Peanuts improve blood glutathione, HDL-cholesterol level and change tissue factor activity in rats fed a high-cholesterol diet. Eur J Nutr. 2007;46(8): 476-82.
  • Emekli-Alturfan E, Kasikci E, Alturfan AA, Pisiriciler R, Yarat A. Effect of sample storage on stability of salivary glutathione, lipid peroxidation levels, and tissue factor activity. J Clin Lab Anal. 2009;23(2): 93-98.
  • Emekli-Alturfan E, Basar I, Malali E, Elemek E, Oktay S, Ayan F, Emekli N, Noyan U. Plasma tissue factor levels and salivary tissue factor activities of periodontitis patients with and without cardiovascular disease. Pathophysiol Haemost Thromb. 2010;37(2-4): 77-81.
  • Emekli-Alturfan E, Kasikci E, Yarat A. Effects of oleic acid on the tissue factor activity, blood lipids, antioxidant and oxidant parameters of streptozotocin induced diabetic rats fed a high-cholesterol diet. Med Chem Res. 2010;19(8): 1011-1024.
  • Tremoli E, Camera M, Toschi V, Colli S. Tissue factor in atherosclerosis. Atherosclerosis. 1999;144: 273-83.
  • Morrissey JH. Tissue factor and factor VII initiation of coagulation. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, editors. Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 89-102.
  • Patterson C, Stouffer GA, Madamanchi N, Runge MS. New tricks for old dogs: non-thrombotic effects of thrombin in vessel wall biology. Circ Res. 2001;88: 987-97.
  • Larsson PT, Schwieler JH, Wallen NH. Platelet activation during angiotensin II infusion in healthy volunteers. Blood Coagul Fibrinolysis. 2000;11: 61-9.
  • Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12: 151-180.
  • Faillace MP, Cutrera R, Keller-Sarmento MI, Rosenstein RE. Evidence for local synthesis of melatonin in golden hamster retina. Neuroreport 1995;6: 2093-2095.
  • Bubenik GA. Gastrointestinal melatonin: localization, function and clinical relevance. Dig Dis Sci. 2002;47: 2336-2348.
  • Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni GJM. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000;28: 193-202.
  • Carrillo-Vico A, Calvo JR, Abreu P, Lardone PJ, Garcia-Morino S, Reiter RJ, Guerrero JM. Evidence of melatonin synthesis in human lymphocytes and its physiological significance: possible role as intracrine, autocrine and/or paracrine substance. FASEB J. 2004;18: 537-539.
  • Hattori A, Migitaka H, Iigo M, Itoh M, Yamamoto K, Oktani-Kandro R, Hara M, Suzuki T, Reiter RJ. Identification of melatonin in plants: its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates. Biochem Mol Biol Int. 1995;35: 627-634.
  • Seweynek E. Melatonin and the cardiovascular system. Neuro Endocrinol Lett. 2002;Suppl 1: 79-83.
  • Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999;83: 1417-1419.
  • Reiter RJ, Tan DX, Pilar TM, Flores LJ, Czarnaocki. Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions. Acta Biochim Pol. 2007;54: 1-9.
  • Pang CS, Xi SC, Brown GM, Pang SF, Shiu SY. 2[125I] Iodomelatonin binding and interaction with beta-adrenergic signaling in chick heart/coronary artery physiology. J Pineal Res. 2002;32: 243-252.
  • Masana MI, Doolen S, Ersahin C, Al-Ghoul WM, Duckles SP. MT(2) melatonin receptors are present and functional in rat caudal artery. J Pharmacol Exp Ther. 2002;302: 1295-1302.
  • Tunali T, Sener G, Yarat A, Emekli N. Melatonin reduces oxidative damage to skin and normalizes blood coagulation in a rat model of thermal injury. Life Sci. 2005;28;76(11): 1259-65.
  • Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine. 2005;27: 189-200.
  • Erşahin M, Sehirli O, Toklu HZ, Süleymanoglu S, Emekli-Alturfan E, Yarat A, Tatlidede E, Yeğen BC, Sener G. Melatonin improves cardiovascular function and ameliorates renal, cardiac and cerebral damage in rats with renovascular hypertension. J Pineal Res. 2009;47(1): 97-106.
  • Navar IG, Harrison-Bernard IM, Nishiyama A, Kobori H. Regulation of intrarenal angiotensin II in hypertension. Hypertension. 2002;39: 316- 322.
  • Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on Experimental Hypertension I. The production of persistent elevation of the systolic blood pressure by means of renal ischemia. J Exper Med. 1934;59: 347-379.
  • Ingram GIC & Hills M. Reference method for the one stage prothrombin time test on human blood. Thromb Haemostas. 1976;36: 237-238.
  • Textor SC, Wilcox CS. Renal artery stenosis: a common, treatable cause of renal failure? Annu Rev Med. 2001;52: 421-442.
  • Magrini F, Reggiani P, Roberts N, Meazza R, Ciulla M, Zanchetti A. Effects of angiotensin and angiotensin blockade on coronary circulation and coronary reserve. Am J Med. 1988;84: 55-60.
  • Kim S, Iwao H. Molecular and cellular mechanisms of angiotensin-II mediated cardiovascular and renal diseases. Pharmacol Rev. 2000;52: 11-34.
  • Minuz P, Patrignani P, Gaino S, Degan M, Menapace L, Tommasoli R, Seta F, Capone ML, Tacconelli S, Palatresi S, Bencini C, Del Vecchio C, Mansueto G, Arosio E, Santonastaso CL, Lechi A, Morganti A, Patrono C. Increased oxidative stress and platelet activation in patients with hypertension and renovascular disease. Circulation. 2002;106: 2800- 2805.
  • Muller DN, Mervaala EMA, Schmidt F, Park JK, Dechend R, Genersch E, Breu V, Löffler BM, Ganten D, Schneider W, Haller H, Luft FC. Effect of bosentan on NF-κB, inflammation, and tissue factor in angiotensin II–induced end-organ damage. Hypertension. 2000;36: 282-290.
  • Ushigome H, Yoshimura N, Sano H, Nakamura K, Oka T. Expression of tissue factor in renal ischemic-reperfusion injury of the rat. Transplant Proc.1998;30: 3764-3765.
  • Wendt T, Zhang YM, Bierhaus A, Kriegsmann J, Deng Y, Waldherr R, Teske T, Luther T, Fünfstück R, Nawroth PP. Tissue factor expression in an animal model of hydronephrosis. Nephrol Dial Transplant. 1995;10: 1820-1828.
  • Maki S, Miyauchi T, Sakai S, Kobayashi T, Maeda S, Takata Y, Sugiyama F, Fukamizu A, Murakami K, Goto K, Sugishita Y. Endothelin-1 expression in hearts of transgenic hypertensive mice. J Cardiovasc Pharmacol. 1998;31: S412-S416.
  • Moreau P, d’Uscio LV, Shaw S, Takase H, Barton M, Luscher TF. Angiotensin II increases tissue endothelin and induces vascular hypertrophy: reversal by ET(A)-receptor antagonist. Circulation. 1997;96: 1593-1597.
  • Lockyer JM, Colladay JS, Alperin-Lea WL, Hammond T, Buda AJ. Inhibition of nuclear factor-κB–mediated adhesion molecule expression in human endothelial cells. Circ Res.1998;82: 314-320.
  • Ferro D, Saliola M, Meroni PL, Valesini G, Caroselli C, Praticò D, Fitzgerald GA, Shoenfeld Y, Violi F. Enhanced monocyte expression of tissue factor by oxidative stress in patients with antiphospholipid antibodies: effect of antioxidant treatment. J Thromb Haemost. 2003; 1(3): 523-531.
  • Ferro D, Basili S, Pratico` D, Iuliano L, FitzGerald GA, Violi F. Vitamin E reduces monocyte tissue factor expression in cirrhotic patients. Blood. 1999; 93: 2945-2950.
There are 43 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Ebru Alturfan

Ayşen Yarat This is me

Göksel Şener This is me

Publication Date January 31, 2014
Submission Date November 17, 2013
Published in Issue Year 2012 Volume: 2 Issue: 2

Cite

APA Alturfan, E., Yarat, A., & Şener, G. (2014). Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri. Clinical and Experimental Health Sciences, 2(2), 78-83.
AMA Alturfan E, Yarat A, Şener G. Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri. Clinical and Experimental Health Sciences. January 2014;2(2):78-83.
Chicago Alturfan, Ebru, Ayşen Yarat, and Göksel Şener. “Deneysel renovasküler Hipertansiyonda Melatoninin böbrek, Kalp Ve Beyin Doku faktörü Aktiviteleri üzerine Etkileri”. Clinical and Experimental Health Sciences 2, no. 2 (January 2014): 78-83.
EndNote Alturfan E, Yarat A, Şener G (January 1, 2014) Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri. Clinical and Experimental Health Sciences 2 2 78–83.
IEEE E. Alturfan, A. Yarat, and G. Şener, “Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri”, Clinical and Experimental Health Sciences, vol. 2, no. 2, pp. 78–83, 2014.
ISNAD Alturfan, Ebru et al. “Deneysel renovasküler Hipertansiyonda Melatoninin böbrek, Kalp Ve Beyin Doku faktörü Aktiviteleri üzerine Etkileri”. Clinical and Experimental Health Sciences 2/2 (January 2014), 78-83.
JAMA Alturfan E, Yarat A, Şener G. Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri. Clinical and Experimental Health Sciences. 2014;2:78–83.
MLA Alturfan, Ebru et al. “Deneysel renovasküler Hipertansiyonda Melatoninin böbrek, Kalp Ve Beyin Doku faktörü Aktiviteleri üzerine Etkileri”. Clinical and Experimental Health Sciences, vol. 2, no. 2, 2014, pp. 78-83.
Vancouver Alturfan E, Yarat A, Şener G. Deneysel renovasküler hipertansiyonda melatoninin böbrek, kalp ve beyin doku faktörü aktiviteleri üzerine etkileri. Clinical and Experimental Health Sciences. 2014;2(2):78-83.

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