Yıl: 2022 Cilt: 30 Sayı: 1 Sayfa Aralığı: 18 - 25 Metin Dili: İngilizce DOI: 10.5606/tgkdc.dergisi.2022.22756 İndeks Tarihi: 15-05-2023

The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta

Öz:
Background: 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.
Anahtar Kelime:

Elabelanın sıçan torasik aortundaki vazorelaksan etkilerinde potasyum kanallarının rolü

Öz:
Amaç: Bu çalışmada, yeni keşfedilen bir endojen apelin reseptör ligandı olan elabelanın vazorelaksan etki mekanizmasında potasyum kanal alt tiplerinin rolü araştırıldı. Ça lışma planı: Yirmi erkek Wistar Albino sıçanın torasik aortlarından elde edilen vasküler halkalar (4 mm) izole doku banyosu sistemine yerleştirildi. Dinlenim gerimi 1 gr olarak ayarlandı. Dengeleme periyodu (90 dak.) sonrasında aort halkaları 10-5 molar fenilefrin ile kasıldı. Plato fazında aort halkalarına kümülatif olarak (10-10-10-6 molar) Elabela uygulandı. Potasyum kanallarının Elabelanın damar gevşetici etki mekanizmasındaki rolünü belirlemek için spesifik potasyum kanalı alt tip inhibitörlerinin varlığında deneysel protokol tekrarlandı. Bulgular: Elabela konsantrasyon bağımlı olarak vazorelaksasyona neden oldu (p<0.001). Fenilefrin kaynaklı kasılmaya göre maksimum gevşeme seviyesi yaklaşık %51’di. Elabelanın damar gevşetici etki düzeyi, endotelin çıkarılmasından sonra istatistiksel olarak anlamlı düzeyde azaldı (p<0.05). Tetraetilamonyum (1 milimolar), 4-Aminopiridin (1 milimolar), gliburid (10 micromolar) ve baryum klorür (30 micromolar) Elabelanın vazorelaksan etki düzeyini istatistiksel olarak anlamlı düzeyde (sırasıyla; p<0.001, p<0.001, p<0.01 ve p<0.05) azalttı. Bununla birlikte, anandamid (10 micromolar) ve apamin (100 nanomolar) Elabelanın vazorelaksan etki seviyesini istatistiksel olarak anlamlı bir şekilde değiştirmedi. So nuç: Bulgularımız büyük iletkenlikli kalsiyum ile aktive olan voltaj kapılı, adenozin trifosfata duyarlı ve içeri doğrultucu potasyum kanallarının Elabelanın sıçan torasik aortundaki damar gevşetici etki mekanizmasında rol oynadığını göstermektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Read C, Nyimanu D, Williams TL, Huggins DJ, Sulentic P, Macrae RGC, et al. International Union of Basic and Clinical Pharmacology. CVII. Structure and pharmacology of the Apelin receptor with a recommendation that Elabela/Toddler is a second endogenous peptide ligand. Pharmacol Rev 2019;71:467-502.
  • 2. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998;251:471-6.
  • 3. Zhang Y, Wang Y, Lou Y, Luo M, Lu Y, Li Z, et al. Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin. Peptides 2018;109:23-32.
  • 4. Xu J, Chen L, Jiang Z, Li L. Biological functions of Elabela, a novel endogenous ligand of APJ receptor. J Cell Physiol 2018;233:6472-82.
  • 5. Chng SC, Ho L, Tian J, Reversade B. ELABELA: A hormone essential for heart development signals via the apelin receptor. Dev Cell 2013;27:672-80.
  • 6. Pauli A, Norris ML, Valen E, Chew GL, Gagnon JA, Zimmerman S, et al. Toddler: An embryonic signal that promotes cell movement via Apelin receptors. Science 2014;343:1248636.
  • 7. İşbil N, Şahintürk S, Demirel S. Vascular functional effects of the apelinergic system. J Lit Pharm Sci 2021;10:12-20.
  • 8. Tykocki NR, Boerman EM, Jackson WF. Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles. Compr Physiol 2017;7:485-581.
  • 9. Jackson WF. Potassium channels in regulation of vascular smooth muscle contraction and growth. Adv Pharmacol 2017;78:89-144.
  • 10. Xu C. The Elabela in hypertension, cardiovascular disease, renal disease, and preeclampsia: An update. J Hypertens 2021;39:12-22.
  • 11. Cheng J, Wen J, Wang N, Wang C, Xu Q, Yang Y. Ion channels and vascular diseases. Arterioscler Thromb Vasc Biol 2019;39:e146-e156.
  • 12. Panthiya L, Pantan R, Tocharus J, Nakaew A, Suksamrarn A, Tocharus C. Endothelium-dependent and endothelium- independent vasorelaxant effects of tiliacorinine 12'-O-acetate and mechanisms on isolated rat aorta. Biomed Pharmacother 2019;109:2090-9.
  • 13. Sahinturk S, Demirel S, Ozyener F, Isbil N. [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels. Gen Physiol Biophys 2021;40:427-34.
  • 14. Yılmaz A, Elbey B, Yazgan ÜC, Dönder A, Arslan N, Arslan S, et al. Protective effects of caffeic acid phenethyl ester on fluoxetine-induced hepatotoxicity: An experimental study. Biomed Res Int 2016;2016:1247191.
  • 15. Perjés Á, Kilpiö T, Ulvila J, Magga J, Alakoski T, Szabó Z, et al. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Res Cardiol 2016;111:2.
  • 16. Wang Z, Yu D, Wang M, Wang Q, Kouznetsova J, Yang R, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems. Sci Rep 2015;5:8170.
  • 17. Demirel S, Şahintürk S, Işbil N, Özyener F. Irisin relaxes rat thoracic aorta through activating signaling pathways implicating protein kinase C. Turk J Med Sci 2021.
  • 18. Modgil A, Guo L, O'Rourke ST, Sun C. Apelin-13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism. PLoS One 2013;8:e83051.
  • 19. Mughal A, Sun C, O̓Rourke ST. Activation of large conductance, calcium-activated potassium channels by nitric oxide mediates apelin-induced relaxation of isolated rat coronary arteries. J Pharmacol Exp Ther 2018;366:265-73.
  • 20. Mughal A, Sun C, OʼRourke ST. Apelin reduces nitric oxide-induced relaxation of cerebral arteries by inhibiting activation of large-conductance, calcium-activated K channels. J Cardiovasc Pharmacol 2018;71:223-32.
  • 21. Demirel S, Sahinturk S, Isbil N, Ozyener F. Physiological role of K+ channels in irisin-induced vasodilation in rat thoracic aorta. Peptides 2021;147:170685.
  • 22. Ahmad T, Shah AJ, Roberts R. Mechanisms mediating the vasodilatory effects of juglone in porcine isolated coronary artery. Eur J Pharmacol 2020;866:172815.
  • 23. Zhou M, Wu Y. Effects and signaling pathways of Elabela in the cardiovascular system. Peptides 2021;147:170674.
  • 24. Arslan S, Zeytun H, Basuguy E, İbiloğlu İ, Uygun İ, Yılmaz A, et al. Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model: An experimental study. Ulus Travma Acil Cerrahi Derg 2017;23:273-8.
APA ŞAHİNTÜRK S, Isbil Buyukcoskun N (2022). The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. , 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
Chicago ŞAHİNTÜRK Serdar,Isbil Buyukcoskun Naciye The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. (2022): 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
MLA ŞAHİNTÜRK Serdar,Isbil Buyukcoskun Naciye The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. , 2022, ss.18 - 25. 10.5606/tgkdc.dergisi.2022.22756
AMA ŞAHİNTÜRK S,Isbil Buyukcoskun N The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. . 2022; 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
Vancouver ŞAHİNTÜRK S,Isbil Buyukcoskun N The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. . 2022; 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
IEEE ŞAHİNTÜRK S,Isbil Buyukcoskun N "The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta." , ss.18 - 25, 2022. 10.5606/tgkdc.dergisi.2022.22756
ISNAD ŞAHİNTÜRK, Serdar - Isbil Buyukcoskun, Naciye. "The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta". (2022), 18-25. https://doi.org/10.5606/tgkdc.dergisi.2022.22756
APA ŞAHİNTÜRK S, Isbil Buyukcoskun N (2022). The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Türk Göğüs Kalp Damar Cerrahisi Dergisi, 30(1), 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
Chicago ŞAHİNTÜRK Serdar,Isbil Buyukcoskun Naciye The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Türk Göğüs Kalp Damar Cerrahisi Dergisi 30, no.1 (2022): 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
MLA ŞAHİNTÜRK Serdar,Isbil Buyukcoskun Naciye The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Türk Göğüs Kalp Damar Cerrahisi Dergisi, vol.30, no.1, 2022, ss.18 - 25. 10.5606/tgkdc.dergisi.2022.22756
AMA ŞAHİNTÜRK S,Isbil Buyukcoskun N The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Türk Göğüs Kalp Damar Cerrahisi Dergisi. 2022; 30(1): 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
Vancouver ŞAHİNTÜRK S,Isbil Buyukcoskun N The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Türk Göğüs Kalp Damar Cerrahisi Dergisi. 2022; 30(1): 18 - 25. 10.5606/tgkdc.dergisi.2022.22756
IEEE ŞAHİNTÜRK S,Isbil Buyukcoskun N "The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta." Türk Göğüs Kalp Damar Cerrahisi Dergisi, 30, ss.18 - 25, 2022. 10.5606/tgkdc.dergisi.2022.22756
ISNAD ŞAHİNTÜRK, Serdar - Isbil Buyukcoskun, Naciye. "The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta". Türk Göğüs Kalp Damar Cerrahisi Dergisi 30/1 (2022), 18-25. https://doi.org/10.5606/tgkdc.dergisi.2022.22756