Person: İŞBİL, NACİYE
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İŞBİL
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NACİYE
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Publication The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta(Baycinar Medical Publ-baycinar Tibbi Yayincilik, 2022-01-01) ŞAHİNTÜRK, SERDAR; Şahintürk, Serdar; İŞBİL, NACİYE; İşbil, Naciye; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; ACQ-9887-2022Background: This study aims to investigate the roles of potassium channel subtypes in the vasorelaxant effect mechanism of elabela, which is a recently discovered endogenous apelin receptor ligand.Methods: The vascular rings (4-mm) obtained from the thoracic aortas of 20 male Wistar Albino rats were placed into the isolated tissue bath system. The resting tension was set to 1 g. The aortic rings were contracted with 10(-5) molar phenylephrine after the equilibration period (90 min). Elabela was applied cumulatively (10(-10)-10(-6) molar) to the aortic rings in the plateau phase. The experimental protocol was repeated in the presence of specific potassium channel subtype inhibitors to determine the role of potassium channels in the vasorelaxant effect mechanism of elabela.Results: Elabela induced a concentration-dependent vasorelaxation (p<0.001). The maximum relaxation level was approximately 51% according to phenylephrine-induced contraction. Vasorelaxant effect level of elabela statistically significantly decreased after removal of the endothelium (p<0.05). Tetraethylammonium (1 milimolar), 4-Aminopyridine (1 milimolar), glyburide (10 micromolar), and barium chloride (30 micromolar) statistically significantly decreased the vasorelaxant effect level of elabela (p<0.001, p<0.001, p<0.01, and p<0.05 respectively). However, anandamide (10 micromolar) and apamin (100 nanomolar) did not statistically significantly change the vasorelaxant effect level of elabela.Conclusion: Our results suggest that large-conductance calcium-activated, voltage-gated, adenosine triphosphate-sensitive, and inward-rectifier potassium channels are involved in the vasorelaxant effect mechanism of elabela in the rat thoracic aorta.Publication Potassium channels contributes to apelin-induced vasodilation in rat thoracic aorta(Bentham Science Publ Ltd, 2022-01-01) ŞAHİNTÜRK, SERDAR; İŞBİL, NACİYE; DEMİREL, SADETTİN; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-1641-2021; AAH-3460-2021; ACQ-9887-2022Background: Apelin is a newly discovered peptide hormone and originally discovered endogenous apelin receptor ligand. Objective: In this study, we aimed to investigate the possible roles of potassium channel subtypes in the vasorelaxant effect mechanisms of apelin. Methods: The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed into the isolated tissue bath system. The resting tension was set to 2 g. After the equilibration period, the aortic rings were precontracted with 10-5 M phenylephrine (PHE) or 45 mM KCl. Pyroglutamyl-apelin-13 ([Pyr1]apelin-13), which is the dominant apelin isoform in the human cardiovascular tissues and human plasma, was applied cumulatively (10(-10)-10(-6) M) to the aortic rings in the plateau phase. The experimental protocol was repeated in the presence of specific K+ channel subtype blockers to determine the role of K(+)channels in the vasorelaxant effect mechanisms of apelin. Results: [Pyr1]apelin-13 induced a concentration-dependent vasorelaxation (p < 0.001). The maximum relaxation level was approximately 52%, according to PHE-induced contraction. Tetraethylammonium, iberiotoxin, 4-Aminopyridine, glyburide, anandamide, and BaCl2 statistically significantly decreased the vasorelaxant effect level of [Pyr1]apelin-13 (p < 0.001). However, apamin didn't statistically significantly change the vasorelaxant effect level of [Pyr1]apelin-13. Conclusion: In conclusion, our findings suggest that BKCa, IKCa, Kv, K-ATP, Kir, and K-2P channels are involved in the vasorelaxant effect mechanisms of apelin in the rat thoracic aorta.Publication Vascular functional effect mechanisms of elabela in rat thoracic aorta(Elsevier Science Inc, 2022-08-01) Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; ÖZYENER, FADIL; Demirel, Sadettin; İŞBİL, NACİYE; DEMİREL, SADETTİN; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-3460-2021; AAH-1641-2021; ACQ-9887-2022Background: Elabela is a recently discovered peptide hormone. The present study aims to investigate the vasorelaxant effect mechanisms of elabela in the rat thoracic aorta.Methods: The vascular rings obtained from the thoracic aortas of the male Wistar albino rats were placed in the isolated tissue bath system. Resting tension was set to 1 gram. After the equilibration period, the vessel rings were contracted with phenylephrine or potassium chloride. Once a stable contraction was achieved, elabela-32 was applied cumulatively (10(-9)-10(-6) molar) to the vascular rings. The experimental protocol was repeated in the presence of specific signaling pathway inhibitors or potassium channel blockers to determine the effect mechanisms of elabela.Results: Elabela showed a significant vasorelaxant effect in a concentration-dependent manner (P < 0.001). The vasorelaxant effect level of elabela was significantly reduced by the apelin receptor antagonist F13A, cyclooxygenase inhibitor indomethacin, adenosine monophosphate-activated protein kinase inhibitor dorsomorphin, protein kinase C inhibitor bisindolmaleimide, large-conductance calcium-activated potassium channel blocker iberiotoxin, and intermediate-conductance calcium-activated potassium channel blocker TRAM-34 (P < 0.001). However, the vasorelaxant effect level of elabela was not significantly affected by the endothelial nitric oxide synthase inhibitor nitro-L-arginine methyl ester and mitogen-activated protein kinase inhibitor U0126.Conclusions: Elabela exhibits a prominent vasodilator effect in rat thoracic aorta. Apelin receptor, prostanoids, adenosine monophosphate-activated protein kinase, protein kinase C, and calcium-activated potassium channels are involved in the vasorelaxant effect mechanisms of elabela.Publication Irisin dilates the rat thoracic aorta via pkc, mek1/2 signaling pathway, kv channels, skca channels, and bkca channels(Wiley, 2022-02-01) Demirel, Sadettin; Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; İşbil, Naciye; İŞBİL, NACİYE; Özyener, Fadil; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-1641-2021; AAH-3460-2021; ACQ-9887-2022Publication [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels(Aepress Sro, 2021-01-01) Şahintürk, Serdar; Demirel, Sadettin; Özyener, Fadıl; İşbil, Naciye; ŞAHİNTÜRK, SERDAR; DEMİREL, SADETTİN; ÖZYENER, FADIL; İŞBİL, NACİYE; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; 0000-0002-7612-0055; 0000-0002-3629-5344; 0000-0002-4606-6596; AAH-3460-2021; ACQ-9887-2022; AAH-1641-2021; FBW-7104-2022In this study, the effect and effect mechanisms of [Pyr1]apelin-13, the dominant apelin isoform in the human cardiovascular tissues and human plasma, on vascular contractility were investigated. The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed in the isolated tissue bath system. After the equilibration period, [Pyr1]apelin-13 (10(-9) to 10(-6) M) was applied cumulatively to the aortic rings pre-contracted with phenylephrine in the plateau phase. The protocol was repeated in the presence of specific signaling pathway inhibitors (F13A, L-NAME, dorsomorphin, TEA, U0126, or indomethacin) to determine the effect mechanisms of [Pyr1]apelin-13. [Pyr1]apelin-13 induced a dose-dependent relaxation in the pre-contracted aortic rings. APJ, eNOS, AMPK, and potassium channel inhibition statistically significantly decreased the vasodilator effect of [Pyr1]apelin-13. MAPK and COX inhibition didn't statistically significantly changed the vasodilator effect of [Pyr1]apelin-13. In conclusion, [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels.Publication Irisin relaxes rat thoracic aorta: MEK1/2 signaling pathway, KV channels, SKCa channels, and BKCa channels are involved in irisin-induced vasodilation(Canadian Science Publishing, 2021-11-26) Demirel, Sadettin; Şahintürk, Serdar; İşbil, Naciye; Özyener, Fadıl; DEMİREL, SADETTİN; ŞAHİNTÜRK, SERDAR; İŞBİL, NACİYE; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; ACQ-9887-2022; AAH-1641-2021; AAH-3460-2021; FBW-7104-2022This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium (K-V) channels, small-conductance calcium-activated potassium (SKCa) channels, and large-conductance calcium-activated potassium (BKCa) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with 10(-5) M phenylephrine (PHE), and then the concentration-dependent responses of irisin (10(-9) -10(-)(6) M) were examined in endothelium-intact and -denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh) - mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10(-8), 10(-7). and 10(-6) M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 mu M for 30 min) augmented ACh-mediated (10(-9)-10(-5)) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated (10(-5)-10(-5)) contraction. In addition, MEK1/2 inhibitor U0126, K-V channel blocker XE-991, SKCa channel blocker apamin, and BKCa channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, K-V channels, and calcium-activated K+ (SKCa and BKCa) channels.Publication [pyr1] apelin-13 exerts vasorelaxant effect in the rat thoracic aorta via APJ, NO, AMPK, and potassium channels(Wiley, 2022-02-01) Şahintürk, Serdar; Demirel, Sadettin; Özyener, Fadıl; İşbil, Naciye; ŞAHİNTÜRK, SERDAR; DEMİREL, SADETTİN; ÖZYENER, FADIL; İŞBİL, NACİYE; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; ACQ-9887-2022; AAH-3460-2021; AAH-1641-2021; FBW-7104-2022Publication Physiological role of K+ channels in irisin-induced vasodilation in rat thoracic aorta(Elsevier Science, 2022-01) Demirel, Sadettin; Şahinturk, Serdar; İşbil, Naciye; Özyener, Fadıl; DEMİREL, SADETTİN; ŞAHİNTÜRK, SERDAR; İŞBİL, NACİYE; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Bölümü; 0000-0002-7612-0055; 0000-0002-4606-6596; 0000-0002-3629-5344; JAQ-7571-2023; ACQ-9887-2022; FBW-7104-2022; AAH-1641-2021Irisin, an exercise-induced myokine, has been shown to have a peripheral vasodilator effect. However, little is known about the mechanisms underlying its effects. In this study, it was aimed to investigate the vasoactive effects of irisin on rat thoracic aorta, and the hypothesis that voltage-gated potassium (KV) channels, ATPsensitive potassium (KATP) channels, small-conductance calcium-activated potassium (SKCa) channels, largeconductance calcium-activated potassium (BKCa) channels, intermediate-conductance calcium-activated potassium (IKCa) channels, inward rectifier potassium (Kir) channels, and two-pore domain potassium (K2P) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with both 10-5 M phenylephrine and 45 mM KCl, and then the concentration-dependent responses of irisin (10-9-10-6 M) were examined. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10-8, 10-7, and 10-6 M (p < 0.001). Besides, KV channel blocker 4-aminopyridine, KATP channel blocker glibenclamide, SKCa channel blocker apamin, BKCa channel blockers tetraethylammonium and iberiotoxin, IKCa channel blocker TRAM-34, and Kir channel blocker barium chloride incubations significantly inhibited the irisin-induced relaxation responses. However, incubation of K2P TASK-1 channel blocker anandamide did not cause a significant decrease in the relaxation responses of irisin. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. Furthermore, this study is the first to report that irisin-induced relaxation responses are associated with the activity of KV, KATP, SKCa, BKCa, IKCa, and Kir channels.