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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Potassium Channels Contributes to Apelin-induced Vasodilation in Rat Thoracic Aorta

Author(s): Serdar Sahinturk*, Sadettin Demirel, Naciye Isbil and Fadil Ozyener

Volume 29, Issue 6, 2022

Published on: 28 June, 2022

Page: [538 - 549] Pages: 12

DOI: 10.2174/0929866529666220516141317

Price: $65

Abstract

Background: 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, KATP, Kir, and K2P channels are involved in the vasorelaxant effect mechanisms of apelin in the rat thoracic aorta.

Keywords: Apelin, potassium channels, thoracic aorta, tissue bath, vasorelaxation, endogenous.

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Graphical Abstract

[1]
Tatemoto, K.; Hosoya, M.; Habata, Y.; Fujii, R.; Kakegawa, T.; Zou, M.X.; Kawamata, Y.; Fukusumi, S.; Hinuma, S.; Kitada, C.; Kurokawa, T.; Onda, H.; Fujino, M. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem. Biophys. Res. Commun., 1998, 251(2), 471-476.
[http://dx.doi.org/10.1006/bbrc.1998.9489] [PMID: 9792798]
[2]
Marsault, E.; Llorens-Cortes, C.; Iturrioz, X.; Chun, H.J.; Lesur, O.; Oudit, G.Y.; Auger-Messier, M. The apelinergic system: A perspective on challenges and opportunities in cardiovascular and metabolic disorders. Ann. N. Y. Acad. Sci., 2019, 1455(1), 12-33.
[http://dx.doi.org/10.1111/nyas.14123] [PMID: 31236974]
[3]
Zhang, Y.; Wang, Y.; Lou, Y.; Luo, M.; Lu, Y.; Li, Z.; Wang, Y.; Miao, L. Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin. Peptides, 2018, 109, 23-32.
[http://dx.doi.org/10.1016/j.peptides.2018.09.006] [PMID: 30267732]
[4]
Maguire, J.J.; Kleinz, M.J.; Pitkin, S.L.; Davenport, A.P. [Pyr1]apelin-13 identified as the predominant apelin isoform in the human heart: Vasoactive mechanisms and inotropic action in disease. Hypertension, 2009, 54(3), 598-604.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.134619] [PMID: 19597036]
[5]
Zhen, E.Y.; Higgs, R.E.; Gutierrez, J.A. Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma. Anal. Biochem., 2013, 442(1), 1-9.
[http://dx.doi.org/10.1016/j.ab.2013.07.006] [PMID: 23872001]
[6]
Mughal, A.; O’Rourke, S.T. Vascular effects of apelin: Mechanisms and therapeutic potential. Pharmacol. Ther., 2018, 190, 139-147.
[http://dx.doi.org/10.1016/j.pharmthera.2018.05.013] [PMID: 29807055]
[7]
Read, C.; Nyimanu, D.; Williams, T.L.; Huggins, D.J.; Sulentic, P.; Macrae, R.G.C.; Yang, P.; Glen, R.C.; Maguire, J.J.; Davenport, A.P. 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(4), 467-502.
[http://dx.doi.org/10.1124/pr.119.017533] [PMID: 31492821]
[8]
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(5), 427-434.
[http://dx.doi.org/10.4149/gpb_2021028] [PMID: 34602456]
[9]
Cheng, J.; Wen, J.; Wang, N.; Wang, C.; Xu, Q.; Yang, Y. Ion channels and vascular diseases. Arterioscler. Thromb. Vasc. Biol., 2019, 39(5), e146-e156.
[http://dx.doi.org/10.1161/ATVBAHA.119.312004] [PMID: 31017824]
[10]
Jackson, W.F. Potassium channels in regulation of vascular smooth muscle contraction and growth. Adv. Pharmacol., 2017, 78, 89-144.
[http://dx.doi.org/10.1016/bs.apha.2016.07.001] [PMID: 28212804]
[11]
Tykocki, N.R.; Boerman, E.M.; Jackson, W.F. Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles. Compr. Physiol., 2017, 7(2), 485-581.
[http://dx.doi.org/10.1002/cphy.c160011] [PMID: 28333380]
[12]
Wysocka, M.B.; Pietraszek-Gremplewicz, K.; Nowak, D. The role of apelin in cardiovascular diseases, obesity and cancer. Front. Physiol., 2018, 9, 557.
[http://dx.doi.org/10.3389/fphys.2018.00557] [PMID: 29875677]
[13]
Loh, Y.C.; Tan, C.S.; Ch’ng, Y.S.; Ahmad, M.; Asmawi, M.Z.; Yam, M.F. Overview of antagonists used for determining the mechanisms of action employed by potential vasodilators with their suggested signaling pathways. Molecules, 2016, 21(4), 495.
[http://dx.doi.org/10.3390/molecules21040495] [PMID: 27092479]
[14]
Tan, C.S.; Loh, Y.C.; Tew, W.Y.; Yam, M.F. Vasorelaxant effect of 3,5,4′-trihydroxy-trans-stilbene (resveratrol) and its underlying mechanism. Inflammopharmacology, 2020, 28(4), 869-875.
[http://dx.doi.org/10.1007/s10787-019-00682-6] [PMID: 31925617]
[15]
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, 2090-2099.
[http://dx.doi.org/10.1016/j.biopha.2018.11.062] [PMID: 30551466]
[16]
Demirel, S.; Sahinturk, S.; Isbil, N.; Ozyener, F. Physiological role of K+ channels in irisin-induced vasodilation in rat thoracic aorta. Peptides, 2022, 147170685
[http://dx.doi.org/10.1016/j.peptides.2021.170685] [PMID: 34748790]
[17]
Sahinturk, S.; Isbil, N. The role of potassium channels on vasorelaxant effects of elabela in rat thoracic aorta. Turk Gogus Kalp Dama., 2022, 30(1), 18-25.
[http://dx.doi.org/10.5606/tgkdc.dergisi.2022.22756]
[18]
Modgil, A.; Guo, L.; O’Rourke, S.T.; 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(12)e83051
[http://dx.doi.org/10.1371/journal.pone.0083051] [PMID: 24386141]
[19]
Kagiyama, S.; Fukuhara, M.; Matsumura, K.; Lin, Y.; Fujii, K.; Iida, M. Central and peripheral cardiovascular actions of apelin in conscious rats. Regul. Pept., 2005, 125(1-3), 55-59.
[http://dx.doi.org/10.1016/j.regpep.2004.07.033] [PMID: 15582714]
[20]
Tatemoto, K.; Takayama, K.; Zou, M.X.; Kumaki, I.; Zhang, W.; Kumano, K.; Fujimiya, M. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul. Pept., 2001, 99(2-3), 87-92.
[http://dx.doi.org/10.1016/S0167-0115(01)00236-1] [PMID: 11384769]
[21]
Mughal, A.; Sun, C.; O’Rourke, S.T. 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(2), 265-273.
[http://dx.doi.org/10.1124/jpet.118.248682] [PMID: 29773582]
[22]
Salcedo, A.; Garijo, J.; Monge, L.; Fernández, N.; Luis García-Villalón, A.; Sánchez Turrión, V.; Cuervas-Mons, V.; Diéguez, G. Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids. Regul. Pept., 2007, 144(1-3), 50-55.
[http://dx.doi.org/10.1016/j.regpep.2007.06.005] [PMID: 17628718]
[23]
Wang, Z.; Yu, D.; Wang, M.; Wang, Q.; Kouznetsova, J.; Yang, R.; Qian, K.; Wu, W.; Shuldiner, A.; Sztalryd, C.; Zou, M.; Zheng, W.; Gong, D.W. Elabela-apelin receptor signaling pathway is functional in mammalian systems. Sci. Rep., 2015, 5(1), 8170.
[http://dx.doi.org/10.1038/srep08170] [PMID: 25639753]
[24]
Katugampola, S.D.; Maguire, J.J.; Matthewson, S.R.; Davenport, A.P. [(125)I]-(Pyr(1)Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. Br. J. Pharmacol., 2001, 132(6), 1255-1260.
[http://dx.doi.org/10.1038/sj.bjp.0703939] [PMID: 11250876]
[25]
Baranowska, M.; Kozłowska, H.; Korbut, A.; Malinowska, B. Potassium channels in blood vessels: Their role in health and disease. Postepy Hig. Med. Dosw., 2007, 61, 596-605.
[PMID: 17971762]
[26]
Hald, B.O.; Jacobsen, J.C.B.; Braunstein, T.H.; Inoue, R.; Ito, Y.; Sørensen, P.G.; Holstein-Rathlou, N-H.; Jensen, L.J.B.K. BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles. Pflugers Arch., 2012, 463(2), 279-295.
[http://dx.doi.org/10.1007/s00424-011-1049-8] [PMID: 22052159]
[27]
Romero, F.; Palacios, J.; Jofré, I.; Paz, C.; Nwokocha, C.R.; Paredes, A.; Cifuentes, F. Aristoteline, an indole-alkaloid, induces relaxation by activating potassium channels and blocking calcium channels in isolated rat aorta. Molecules, 2019, 24(15), 2748.
[http://dx.doi.org/10.3390/molecules24152748] [PMID: 31362388]
[28]
Dong, D.L.; Bai, Y.L.; Cai, B.Z. Calcium-activated potassium channels: Potential target for cardiovascular diseases. Adv. Protein Chem. Struct. Biol., 2016, 104, 233-261.
[http://dx.doi.org/10.1016/bs.apcsb.2015.11.007] [PMID: 27038376]
[29]
Mughal, A.; Sun, C. OʼRourke, S.T. Apelin reduces nitric oxide-induced relaxation of cerebral arteries by inhibiting activation of large-conductance, calcium-activated K channels. J. Cardiovasc. Pharmacol., 2018, 71(4), 223-232.
[http://dx.doi.org/10.1097/FJC.0000000000000563] [PMID: 29620606]
[30]
Nieves-Cintrón, M.; Syed, A.U.; Nystoriak, M.A.; Navedo, M.F. Regulation of voltage-gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders. Microcirculation, 2018, 25(1)e12423
[http://dx.doi.org/10.1111/micc.12423] [PMID: 29044853]
[31]
Ko, E.A.; Han, J.; Jung, I.D.; Park, W.S. Physiological roles of K+ channels in vascular smooth muscle cells. J. Smooth Muscle Res., 2008, 44(2), 65-81.
[http://dx.doi.org/10.1540/jsmr.44.65] [PMID: 18552454]
[32]
Nelson, M.T.; Quayle, J.M. Physiological roles and properties of potassium channels in arterial smooth muscle. Am. J. Physiol., 1995, 268(4 Pt 1), C799-C822.
[http://dx.doi.org/10.1152/ajpcell.1995.268.4.C799] [PMID: 7733230]
[33]
Tajada, S.; Cidad, P.; Moreno-Domínguez, A.; Pérez-García, M.T.; López-López, J.R. High blood pressure associates with the remodelling of inward rectifier K+ channels in mice mesenteric vascular smooth muscle cells. J. Physiol., 2012, 590(23), 6075-6091.
[http://dx.doi.org/10.1113/jphysiol.2012.236190] [PMID: 22966162]
[34]
Gardener, M.J.; Johnson, I.T.; Burnham, M.P.; Edwards, G.; Heagerty, A.M.; Weston, A.H. Functional evidence of a role for two-pore domain potassium channels in rat mesenteric and pulmonary arteries. Br. J. Pharmacol., 2004, 142(1), 192-202.
[http://dx.doi.org/10.1038/sj.bjp.0705691] [PMID: 15066906]

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