Bülent IŞIK, Raviye ÖZEN KOCA, Z. Işık SOLAK GÖRMÜŞ, Hatice SOLAK, Ayşe ÖZDEMİR, Arzu EMEKSİZ

Fluoksetinin sıçan torasik aort düz kasındaki vazoaktif etkileri

Amaç: Literatürdeki çalışmaların çoğu fluoksetinin kardiyo/serebrovasküler sistemler üzerindeki etkilerine odaklanmış olsa da, vazomotor etkisi hakkında bilinenler hala sınırlıdır. Bu çalışma, fluoksetinin sıçan torasik aort halkalarında düz kas üzerindeki vazoaktif etkilerini deneysel bir düzende araştırmak için planlanmıştır. Gereç ve Yöntem: 24 adet yetişkin Wistar albino rat iki gruba ayrıldı. Grup1-Endotel sağlam grup, Grup2-Endotel hasarlı grup. Servikal dislokasyon sonrası torasik aort izole edildi. Aort halkaları hemen Krebs solüsyonu içeren organ banyosu haznelerine yerleştirildi. Aort halkalarının izometrik gerimindeki değişiklikler kaydedildi. Fenilefrin 10-6M uygulandı ve kasılmalar kaydedildi. Daha sonra Grup 1'e kümülatif dozlarda (0.01, 0.1, 1, 2 mM) fluoksetin uygulandı. Grup 2'de endotel hasarı oluşturuldu. Asetilkolin 10-6M ile endotel hasarı kontrol edildikten sonra, halkalar bir saat yıkanarak ikinci doz fenilefrin hazneye eklendi. Ardından Grup 2'ye kümülatif olarak fluoksetin uygulanıp kasılmalar kaydedildi. Bulgular: Fluoksetinin doza bağımlı ana vazodilatör etkisi anlamlı olarak farklıyken [F (5.110) =72.740, p

Vasoactive effects of fluoxetine in rat thoracic aorta smooth muscle

Purpose: While most studies of fluoxetine have focused on its effects on the cardio/cerebrovascular systems, what is known about its vasomotor effect is still limited. This study was planned to investigate the vasoactive effects of fluoxetine on smooth muscle in rat thoracic aortic rings in an experimental setup. Materials and Methods: 24 adult Wistar albino rats were divided into two groups. Group1-Endothelium intact group, Group2-Endothelium damaged group. Descending thoracic aorta was isolated after cervical dislocation. The aorta rings were immediately placed in organ bath chambers containing Krebs solution. Changes in isometric tension of aorta rings were recorded. Phenylephrine 10-6M was administered and contractions were recorded in groups. Then, fluoxetine was given to Group 1 in cumulative doses (0.01, 0.1, 1, 2 mM). Endothelial damage was created in Group 2. After controlling the endothelial damage by acetylcholine 10-6M, rings were washed for an hour and a second dose of phenylephrine was administered and then fluoxetine was given cumulatively to Group 2 and contractions were recorded. Results: While the dose-dependent main vasodilator effect of fluoxetine was significantly different [F (5.110) =72.740, p

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1. Zellweger MJ, Osterwalder RH, Langewitz W, Pfisterer ME. Coronary artery disease and depression. Eur Heart J. 2004;25:3-9.
2. Taylor CB, Youngblood ME, Catellier D, Veith RC, Carney RM, Brug MM et al. Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch Gen Psychiatry. 2005;62:792-98.
3. Goldston K, Baillie AJ. Depression and coronary heart disease: a review of the epidemiological evidence, explanatory mechanisms and management approaches. Clin Psychol Rev. 2008;28:288-306.
4. Baldwin D, Rudge S. The role of serotonin in depression and anxiety. Int Clin Psychopharmacol. 1995;9:41–5.
5. Schins A, Hamulyák K, Scharpé S, Lousberg R, Van Melle JV, Crijns H et al. Whole blood serotonin and platelet activation in depressed post-myocardial infarction patients. Life Sci. 2004;76:637-50.
6. Alvarez JC, Gluck N, Arnulf I, Quintin P, Leboyer M, Pecquery R et al. Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine. Clin Pharmacol Ther. 1999;66:617-24.
7. Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994;40:288-95.
8. Fidan E, Gormus ZIS, Kilinc I, İyisoy MS, Gormus N. Effects of combined sertraline and magnesium in rat atrium. Biol Trace Elem Res. 2022;200:652-60.
9. Hiemke C, Härtter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther. 2000;85:11-28.
10. Catterson ML, Preskorn SH. Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance. Pharmacol Toxicol. 1996;78:203-8.
11. García-Colunga J, Awad JN, Miledi R. Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (Prozac). Proc Natl Acad Sci U S A. 1997;94:2041-4.
12. Choi JS, Hahn SJ, Rhie DJ, Yoon SH, Jo YH, Kim MS. Mechanism of fluoxetine block of cloned voltageactivated potassium channel Kv1.3. J Pharmacol Exp Ther. 1999;291:1-6.
13. Tytgat J, Maertens C, Daenens P. Effect of fluoxetine on a neuronal, voltage-dependent potassium channel (Kv1.1). Br J Pharmacol. 1997;122:1417-24.
14. Stauderman KA, Gandhi VC, Jones DJ. Fluoxetineinduced inhibition of synaptosomal [3H]5-HT release: possible Ca2+-channel inhibition. Life Sci. 1992;50:2125-38.
15. Farrugia G. Modulation of ionic currents in isolated canine and human jejunal circular smooth muscle cells by fluoxetine. Gastroenterology. 1996;110:1438-45.
16. Pitt BR, Weng W, Steve AR, Blakely RD, Reynolds I, Davies P. Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular smooth muscle cells in culture. Am J Physiol. 1994;266:178- 86.
17. Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation. 2001;104:1894-8.
18. Paraskevaidis I, Parissis JT, Fountoulaki K, Filippatos G, Kremastinos D. Selective serotonin re-uptake inhibitors for the treatment of depression in coronary artery disease and chronic heart failure: evidence for pleiotropic effects. Cardiovasc Hematol Agents Med Chem. 2006;4:361-7.
19. Pereira CA, Rodrigues FL, Ruginsk SG, Zanotto CZ, Rodrigues JA, Duarte DA et al. Chronic treatment with fluoxetine modulates vascular adrenergic responses by inhibition of pre- and post-synaptic mechanisms. Eur J Pharmacol. 2017;800:70-80.
20. Nurullahoğlu-Atalık KE, Kutlu S, Solak H, Koca RÖ. Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging. Physiol Int. 2017;104:226-34.
21. Dogan M, Peker RO, Donmez S, Gokalp O. Magnesium and diltiazem relaxes phenylephrineprecontracted rat aortic rings. Interact Cardiovasc Thorac Surg. 2012;15:1-4.
22. Cohen J. A power primer. Psychol Bull. 1992;112:155- 9.
23. Gan Y, Gong Y, Tong X, Sun H, Cong Y, Dong X et al. Depression and the risk of coronary heart disease: a meta-analysis of prospective cohort studies. BMC Psychiatry. 2014;14:371.
24. Pizzi C, Rutjes AW, Costa GM, Fontana F, Mezzetti A, Manzoli L. Meta-analysis of selective serotonin reuptake inhibitors in patients with depression and coronary heart disease. Am J Cardiol. 2011;107:972-9.
25. Schlienger RG, Fischer LM, Jick H, Meier CR. Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction. Drug Saf. 2004;27:1157-65.
26. Strik JJ, Honig A, Lousberg R, Lousberg AH, Cheriex EC, Tuynman-Qua HG et al. Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Psychosom Med. 2000;62:783-9.
27. Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger Jr JT et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-9.
28. Glassman AH, Bigger JT, Gaffney M, Shapiro PA, Swenson JR. Onset of major depression associated with acute coronary syndromes: relationship of onset, major depressive disorder history, and episode severity to sertraline benefit. Arch Gen Psychiatry. 2006;63:283-8.
29. van Melle JP, de Jonge P, van den Berg MP, Pot HJ, van Veldhuisen DJ. Treatment of depression in acute coronary syndromes with selective serotonin reuptake inhibitors. Drugs. 2006;66:2095-107.
30. Wong DT, Threlkeld PG, Robertson DW. Affinities of fluoxetine, its enantiomers, and other inhibitors of serotonin uptake for subtypes of serotonin receptors. Neuropsychopharmacology. 1991;5:43-7.
31. Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E et al. Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996;126:234-40.
32. Maggi L, Palma E, Miledi R, Eusebi F. Effects of fluoxetine on wild and mutant neuronal alpha 7 nicotinic receptors. Mol Psychiatry. 1998;3:350-5.
33. Lavoie PA, Beauchamp G, Elie R. Atypical antidepressants inhibit depolarization-induced calcium uptake in rat hippocampus synaptosomes. Can J Physiol Pharmacol. 1997;75:983-7.
34. Maertens C, Wei L, Voets T, Droogmans G, Nilius B. Block by fluoxetine of volume-regulated anion channels. Br J Pharmacol. 1999;126:508-14.
35. Ungvari Z, Pacher P, Kecskeméti V, Koller A. Fluoxetine dilates isolated small cerebral arteries of rats and attenuates constrictions to serotonin, norepinephrine, and a voltage-dependent Ca2+ channel opener. Stroke. 1999;30:1949-54.
36. Akinci M, Karadag CH, Huseyin S, Oltulu C, Canbaz S, Gunduz O et al. Effects of in vitro amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts. Braz J Cardiovasc Surg. 2019;34:290-96.
37. Berends HI, Nijlant J, van Putten M, Movig KLL, IJzerman MJ. Single dose of fluoxetine increases muscle activation in chronic stroke patients. Clin Neuropharmacol. 2009;32:1-5.
38. Moffitt JA, Johnson AK. Short-term fluoxetine treatment enhances baroreflex control of sympathetic nervous system activity after hindlimb unloading. Am J Physiol Regul Integr Comp Physiol. 2004;286:584- 90.
39. Ungvari Z, Tarantini S, Yabluchanskiy A, Csiszar A. Potential adverse cardiovascular effects of treatment with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) in patients with geriatric depression: ımplications for atherogenesis and cerebromicrovascular dysregulation. Front Genet. 2019;10:898.
40. Karson CN, Newton JE, Livingston R, Jolly JB, Cooper TB, Sprigg J et al. Human brain fluoxetine concentrations. J Neuropsychiatry Clin Neurosci. 1993;5:322-9.