Sıçanlarda Vasküler Tonusun Düzenlenmesinde Potasyum Kanallarının Rolünün İncelenmesi

Potasyum (K+) kanalları vasküler tonusun önemli düzenleyicileridir. Bu çalışmada K+ kanal tiplerinin fenilefrin ile uyarılan vasküler tonus üzerindeki etkilerinin belirlenmesi amaçlanmıştır. Wistar Albino ırkı erkek sıçanların torasik aortlarından elde edilen 4 mm uzunluğundaki vasküler halkalar izole organ banyosu sistemine yerleştirildi. Vasküler gerim 1 grama ayarlandı. K+ kanal tiplerinin fenilefrin ile indüklenen vasküler tonus üzerindeki etkilerini belirlemek için, 1 saatlik bir dengeleme döneminden sonra aort halkalarına K+ kanal blokörleri uygulandı. 30 dakikalık inkübasyondan sonra, vasküler halkalar 10-6 M fenilefrin ile kasıldı ve stabil bir kasılma elde edildi. Fenilefrin uygulamalarından önceki dönemlerdeki gerim değerleri %100 olarak kabul edildi. Fenilefrin ile elde edilen plato fazı gerim değerleri bu değer üzerinden hesaplandı. Elde edilen gerim değerleri kontrol gruplarındaki gerim değerleri ile karşılaştırıldı. Büyük iletkenli kalsiyum (Ca2+) ile aktive olan K+ kanal (BKCa) blokörü tetraetilamonyum, orta iletkenli Ca2+ ile aktive olan K+ kanal (IKCa) blokörü TRAM-34, ATP-duyarlı K+ kanal (KATP) blokörü gliburid, voltaj kapılı K+ kanal (KV) blokörü 4-Aminopiridin ve iki porlu K+ kanal (K2P) blokörü anandamid uygulamaları vasküler gerim değerlerinde istatistiksel olarak anlamlı artışa neden oldu. Ancak, küçük iletkenli Ca2+ ile aktive olan K+ kanal (SKCa) blokörü apamin ve içeri doğrultucu K+ kanal (Kir) blokörü baryum klorür uygulamaları vasküler gerim değerlerinde istatistiksel olarak anlamlı bir değişikliğe neden olmadı. Bu çalışmanın bulguları, BKCa, IKCa, KATP, KV ve K2P kanallarının fenilefrin ile indüklenen vasküler tonusun düzenlenmesinde önemli etkilere sahip olduğunu göstermektedir. Öte yandan SKCa ve Kir kanallarının fenilefrin ile indüklenen vasküler tonusun düzenlenmesinde önemli faktörler olmadığı düşünülmektedir.

Anahtar Kelimeler:

Potasyum kanalları, Vasküler tonus, Torasik aort, Doku banyosu

Investigation of the Role of Potassium Channels in the Regulation of Vascular Tone in Rats

Potassium (K+) channels are important regulators of vascular tone. In this study, it was aimed to determine the effects of K+ channel types on phenylephrine-induced vascular tone. The 4 mm length vascular rings obtained from the thoracic aortas of male Wistar Albino rats were placed in the isolated tissue bath system. Vascular tension was adjusted to 1 gram. To determine the effects of K+ channel types on phenylephrine-induced vascular tone, K+ channel blockers were administered to the aortic rings after a 1-hour equilibration period. After 30 min of incubation, the vascular rings were contracted with 10-6 M phenylephrine and a stable contraction was obtained. The tension values in the periods before the phenylephrine administrations were accepted as 100%. The plateau phase tension values obtained with phenylephrine were calculated over this value. The obtained tension values were compared with the tension values in the control groups. Large-conductance calcium (Ca2+)-activated K+ channel (BKCa) blocker tetraethylammonium, intermediate-conductance Ca2+-activated K+ (IKCa) channel blocker TRAM-34, ATP-sensitive K+ (KATP) channel blocker glyburide, voltage-gated K+ (KV) channel blocker 4-Aminopyridine, and two-pore domain K+ (K2P) channel blocker anandamide administrations caused a statistically significant increase in vascular tension values. However, small-conductance Ca2+-activated K+ (SKCa) channel blocker apamin and inwardly-rectifying K+ (Kir) channel blocker barium chloride administrations did not cause a statistically significant change in vascular tension values. The findings of this study show that BKCa, IKCa, KATP, KV, and K2P channels have significant effects on the regulation of phenylephrine-induced vascular tone. On the other hand, it is suggested that SKCa and Kir channels are not important factors in the regulation of phenylephrine-induced vascular tone.

Keywords:

Potassium channels, Vascular tone, Thoracic aort, Tissue bath,

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1. Griffith TM. Modulation of blood flow and tissue perfusion by endothelium-derived relaxing factor. Exp Physiol 1994;79(6):873-913.
2. Bagher P and Segal SS. Regulation of blood flow in the microcirculation: role of conducted vasodilation. Acta Physiol (Oxf) 2011;202(3):271-84.
3. Klabunde RE, (eds). Cardiovascular Physiology Concepts. 3rd edition. Philadelphia: Lippincott Williams & Wilkins, 2021.
4. Klabunde RE, (eds). Cardiovascular Physiology Concepts. 2nd edition. Philadelphia: Lippincott Williams & Wilkins, 2011.
5. Barrett KE, Barman SM, Boitano S, Brooks HL, (eds). Ganong’un Tıbbi Fizyolojisi. 24. Baskı. İstanbul: Nobel Tıp Kitabevleri, 2015.
6. Hall JE, (eds). Guyton ve Hall Tıbbi Fizyoloji. 13. Baskı. Ankara: Güneş Tıp Kitabevleri, 2017.
7. Tykocki NR, Boerman EM, Jackson WF. Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles. Compr Physiol 2017;7(2):485–581.
8. Jackson WF. Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth. Adv Pharmacol 2018;78:89–144.
9. Emre M. Potasyum İyon Kanallarının Yapısı ve Genel Özellikleri. Arşiv Kaynak Tarama Dergisi 2020;29(4):276-90.
10. Dogan MF, Yildiz O, Arslan SO, Ulusoy KG. Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective. Fundam Clin Pharmacol 2019;33:504–23.
11. 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.
12. Hald BO, Jacobsen JCB, Braunstein TH, et al. BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles. Pflug Arch Eur J Physiol 2012;463:279–95.
13. Mughal A, Sun C, O‘Rourke 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.
14. 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(4):223-32.
15. Romero F, Palacios J, Jofré I, et al. Aristoteline, an Indole-Alkaloid, Induces Relaxation by Activating Potassium Channels and Blocking Calcium Channels in Isolated Rat Aorta. Molecules 2019;24(15):2748.
16. Tan CS, Loh YC, Tew WY, Yam MF. Vasorelaxant effect of 3,5,4'-trihydroxy-trans-stilbene (resveratrol) and its underlying mechanism. Inflammopharmacology 2020;28(4):869-75.
17. Ahmad T, Shah AJ, Khan T, Roberts R. Mechanism underlying the vasodilation induced by diosmetin in porcine coronary artery. Eur J Pharmacol 2020;884:173400.
18. Tian C, Zhu R, Zhu L, et al. Potassium Channels: Structures, Diseases, and Modulators. Chem Biol Drug Des 2014;83(1):1–26.
19. Singh S, Agarwal P, Ravichandiran V. Two-Pore Domain Potassium Channel in Neurological Disorders. J Membr Biol 2021;254(4):367–80.
20. Burg S, Attali B. Targeting of Potassium Channels in Cardiac Arrhythmias. Trends Pharmacol Sci 2021;42(6):491–506.
21. Szeto V, Chen NH, Sun HS, Feng ZP. The role of KATP channels in cerebral ischemic stroke and diabetes. Acta Pharmacol Sin 2018;39:683–94.
22. Miao Q, Wang S, Miao S, et al. Cardioprotective Effect of Polydatin against Ischemia/reperfusion Injury: Roles of Protein Kinase C and Mito K(ATP) Activation. Phytomedicine 2011;19(1):8–12.
23. Tirloni CAS, Lívero FADR, Palozi RAC, et al. Ethnopharmacological Investigations of the Cardio-Renal Properties of a Native Species from the Region of Pantanal, State of Mato Grosso Do Sul, Brazil. J Ethnopharmacol 2017;206:125–34.
24. Nieves-Cintrón M, Syed AU, Nystoriak MA, Navedo MF. Regulation of voltage-gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders. Microcirculation 2018;25(1):10.1111/micc.12423.
25. Namgoong H, Chaeeun C, Lee S. The KV7 channel activator, retigabine, induces vasorelaxation via an endothelial-independent pathway in male mouse aorta. J Exerc Nutrition Biochem 2018;22(3):51-5.
26. Khammy MM, Kim S, Bentzen BH, et al. 4-Aminopyridine: a pan voltage-gated potassium channel inhibitor that enhances Kv 7.4 currents and inhibits noradrenaline-mediated contraction of rat mesenteric small arteries. Br J Pharmacol 2018;175(3):501-16.
27. Ko EA, Han J, Jung ID, Park WS. Physiological roles of K+ channels in vascular smooth muscle cells. J Smooth Muscle Res 2008;44(2):65-81.
28. Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 1995;268(4 Pt 1):C799-822.
29. Tajada S, Cidad P, Moreno-Domínguez A, Pérez-García MT, López-López JR. High blood pressure associates with the remodelling of inward rectifier K+ channels in mice mesenteric vascular smooth muscle cells. J Physiol 2012;590(23):6075-91.
30. Gardener MJ, Johnson IT, Burnham MP, Edwards G, Heagerty AM, Weston AH. 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.