Araştırma Makalesi
BibTex RIS Kaynak Göster

Kv7.1-7.5 Kanallarının Sıçan Torasik Aortundaki Apela Kaynaklı Vasorelaksasyondaki Rolü

Yıl 2023, Cilt: 45 Sayı: 5, 639 - 650, 27.09.2023
https://doi.org/10.20515/otd.1261865

Öz

Apela yeni keşfedilen bir hormonal peptiddir. Bu çalışma, Apela'nın damar gevşetici etkilerinde Kv7.1-7.5 kanallarının rolünü sıçan torasik aort modelinde araştırmayı amaçladı. Erkek Wistar Albino sıçanlardan izole edilen 4 mm’lik torasik aort halkaları izole doku banyosu sistemindeki banyo haznelerine yerleştirildi. Dinlenim durumundaki gerim seviyesi 1 gram olarak ayarlandı. 90 dakikalık dengelenme periyodundan sonra, torasik aort halkaları fenilefrin veya potasyum klorür ile kasıldı. Stabil bir kasılma sağlandıktan sonra torasik aort halkalarına kümülatif olarak Apela (10-10-10-6 M) uygulandı. Apela'nın etki mekanizmalarını ortaya koymak için, belirtilen deney protokolü, seçici Kv7.1-7.5 kanal blokörü (XE-991; 30 µM) varlığında tekrarlandı. Apela, konsantrasyona bağlı olarak anlamlı düzeyde damar gevşetici etki gösterdi (p<0,001). Apela'nın damar gevşetici etkisi endotelin çıkarılmasından sonra büyük ölçüde korundu. Apela'nın vazodilatör etki seviyesi sağlam veya çıkarılmış endoteli olan sıçan torasik aort halkalarına seçici Kv7.1-7.5 kanal blokeri XE-991 uygulanmasından sonra istatistiksel olarak anlamlı ölçüde azaldı (p<0,001). Sonuç olarak, Kv7.1-7.5 kanalları Apela'nın damar gevşetici etki mekanizmalarına katkıda bulunmaktadır.

Destekleyen Kurum

FİNANSAL DESTEK ALINMADI.

Proje Numarası

.

Teşekkür

.

Kaynakça

  • 1. 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.
  • 2. Read C, Nyimanu D, Williams TL, 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.
  • 3. Zhang Y, Wang Y, Lou Y, et al. Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin. Peptides. 2018;109:23-32.
  • 4. Zhou M, Wu Y. Effects and signaling pathways of Elabela in the cardiovascular system. Peptides. 2021;27:170674.
  • 5. Jackson WF. Potassium channels in regulation of vascular smooth muscle contraction and growth. Adv Pharmacol. 2018;78:89–144.
  • 6. Bubolz AH, Li H, Wu Q, Liu Y. Enhanced oxidative stress impairs cAMP-mediated dilation by reducing Kv channel function in small coronary arteries of diabetic rats. Am J Physiol Heart Circ Physiol. 2005;289:H1873-80.
  • 7. Cox RH, Fromme SJ, Folander KL, Swanson RJ. Voltage-gated K+ channel expression in arteries of Wistar-Kyoto and spontaneously hypertensive rats. Am J Hypertens. 2008;21:213.
  • 8. Fosmo AL, Skraastad ØB. The Kv7 channel and cardiovascular risk factors. Front Cardiovasc Med. 2017;4:75.
  • 9. Mills TA, Greenwood SL, Devlin G, et al. Activation of Kv7 channels stimulates vasodilatation of human placental chorionic plate arteries. Placenta. 2015;36:638-44.
  • 10. 10. Schleifenbaum J, Köhn C, Voblova N, et al. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 2010;28:1875-82.
  • 11. Zhong XZ, Harhun MI, Olesen SP, et al. Participation of KCNQ (Kv7) potassium channels in myogenic control of cerebral arterial diameter. J Physiol. 2010;588:3277-93.
  • 12. Chadha PS, Zunke F, Davis AJ, et al. Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. Br J Pharmacol. 2012;166:1377–87.
  • 13. Morales-Cano D, Moreno L, Barreira B, et al. Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycemia. Cardiovasc Res. 2015;106:98-108.
  • 14. Chadha PS, Zunke F, Zhu HL, et al. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired beta-adrenoceptor-mediated relaxation of renal arteries in hypertension. Hypertension. 2012;59:877-84.
  • 15. Wang N, Kuczmanski A, Dubrovska G, Gollasch M. Palmitic acid methyl ester and its relation to control of tone of human visceral arteries and rat aortas by perivascular adipose tissue. Front Physiol. 2018;9:583.
  • 16. Mondéjar-Parreño G, Barreira B, Callejo M, et al. Uncovered contribution of kv7 channels to pulmonary vascular tone in pulmonary arterial hypertension. Hypertension. 2020;76:1134-46.
  • 17. Nurullahoğlu-Atalık KE, Kutlu S, Solak H, Özen-Koca R. Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging. Physiol Int. 2017;104:226–34.
  • 18. Sousa-Brito HL, Arruda-Barbosa L, Vasconcelos-Silva AA, et al. Vasorelaxant effect of trans-4-chloro-β-nitrostyrene, a synthetic nitroderivative, in rat thoracic aorta. Fundam Clin Pharmacol. 2021;35:331–40.
  • 19. Yang P, Read C, Kuc RE, et al. Elabela/toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system, and exogenous administration of the peptide compensates for the downregulation of its expression in pulmonary arterial hypertension. Circulation. 2017;135:1160-73.
  • 20. Perjés Á, Kilpiö T, Ulvila J, et al. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Res Cardiol. 2016;111:2.
  • 21. Xu C. The Elabela in hypertension, cardiovascular disease, renal disease, and preeclampsia: an update. J Hypertens. 2021;39:12-22.
  • 22. Murza A, Sainsily X, Coquerel D, et al. Discovery and structure-activity relationship of a bioactive fragment of ELABELA that modulates vascular and cardiac functions. J Med Chem. 2016;59:2962-72.
  • 23. Ho L, van Dijk M, Chye STJ, et al. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. Science. 2017;357:707-13.
  • 24. Li Y, Yang X, Ouyang S, et al. Declined circulating Elabela levels in patients with essential hypertension and its association with impaired vascular function: a preliminary study. Clin Exp Hypertens. 2020;42:239-43.
  • 25. Wang Z, Yu D, Wang M, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems. Sci Rep. 2015;5:8170.
  • 26. Baranowska M, Kozłowska H, Korbut A, Malinowska B. Potassium channels in blood vessels: 10 their role in health and disease. Postepy Hig Med Dosw (Online). 2007;61:596-605.
  • 27. Cheng J, Wen J, Wang N, Wang C, Xu Q, Yang Y. Ion channels and vascular diseases. Arterioscler Thromb Vasc Biol. 2019;39:e146-56.
  • 28. Martelli A, Testai L, Breschi MC, et al. Vasorelaxation by hydrogen sulphide involves activation of Kv7 potassium channels. Pharmacol Res. 2013;70:27-34.
  • 29. Stott JB, Barrese V, Jepps TA, Leighton EV, Greenwood IA. Contribution of kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats. Hypertension. 2015;65:676-82.
  • 30. Jepps TA, Chadha PS, Davis AJ, Harhun MI, Cockerill GW, Olesen SP, et al. Downregulation of Kv7.4 channel activity in primary and secondary hypertension. Circulation. 2011;124:602-11

The Role of Kv7.1-7.5 Channels in Apela-induced Vasorelaxation in the Rat Thoracic Aorta

Yıl 2023, Cilt: 45 Sayı: 5, 639 - 650, 27.09.2023
https://doi.org/10.20515/otd.1261865

Öz

Apela is a recently discovered hormonal peptide. This study aimed to investigate the roles of Kv7.1-7.5 channels in the vasorelaxant effects of Apela in a rat thoracic aortic model. The 4 mm thoracic aortic rings isolated from the male Wistar Albino rats were placed in the bath chambers in the isolated tissue bath system. The resting tension level was adjusted to 1 gram. After the 90 min equilibration period, the thoracic aortic rings were contracted with phenylephrine or potassium chloride. Once a stable contraction was achieved, Apela (10-10-10-6 M) was administered cumulatively to the thoracic aortic rings. To reveal the mechanisms of action of Apela, the specified experimental protocol was repeated in the presence of the selective Kv7.1-7.5 channel blocker (XE-991; 30 µM). Apela showed a significant vasodilatory effect in a concentration-dependent manner (p<0.001). The vasorelaxant effect of Apela was largely preserved after the removal of the endothelium. Apela’s vasodilatory effect level was statistically significantly reduced (p<0.001) after administration of the selective Kv7.1-7.5 channel blocker XE-991 in the thoracic aortic rings of rats with intact or denuded endothelium. In conclusion, Kv7.1-7.5 channels contribute to the vasorelaxant effect mechanisms of Apela.

Proje Numarası

.

Kaynakça

  • 1. 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.
  • 2. Read C, Nyimanu D, Williams TL, 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.
  • 3. Zhang Y, Wang Y, Lou Y, et al. Elabela, a newly discovered APJ ligand: Similarities and differences with Apelin. Peptides. 2018;109:23-32.
  • 4. Zhou M, Wu Y. Effects and signaling pathways of Elabela in the cardiovascular system. Peptides. 2021;27:170674.
  • 5. Jackson WF. Potassium channels in regulation of vascular smooth muscle contraction and growth. Adv Pharmacol. 2018;78:89–144.
  • 6. Bubolz AH, Li H, Wu Q, Liu Y. Enhanced oxidative stress impairs cAMP-mediated dilation by reducing Kv channel function in small coronary arteries of diabetic rats. Am J Physiol Heart Circ Physiol. 2005;289:H1873-80.
  • 7. Cox RH, Fromme SJ, Folander KL, Swanson RJ. Voltage-gated K+ channel expression in arteries of Wistar-Kyoto and spontaneously hypertensive rats. Am J Hypertens. 2008;21:213.
  • 8. Fosmo AL, Skraastad ØB. The Kv7 channel and cardiovascular risk factors. Front Cardiovasc Med. 2017;4:75.
  • 9. Mills TA, Greenwood SL, Devlin G, et al. Activation of Kv7 channels stimulates vasodilatation of human placental chorionic plate arteries. Placenta. 2015;36:638-44.
  • 10. 10. Schleifenbaum J, Köhn C, Voblova N, et al. Systemic peripheral artery relaxation by KCNQ channel openers and hydrogen sulfide. J Hypertens. 2010;28:1875-82.
  • 11. Zhong XZ, Harhun MI, Olesen SP, et al. Participation of KCNQ (Kv7) potassium channels in myogenic control of cerebral arterial diameter. J Physiol. 2010;588:3277-93.
  • 12. Chadha PS, Zunke F, Davis AJ, et al. Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. Br J Pharmacol. 2012;166:1377–87.
  • 13. Morales-Cano D, Moreno L, Barreira B, et al. Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycemia. Cardiovasc Res. 2015;106:98-108.
  • 14. Chadha PS, Zunke F, Zhu HL, et al. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired beta-adrenoceptor-mediated relaxation of renal arteries in hypertension. Hypertension. 2012;59:877-84.
  • 15. Wang N, Kuczmanski A, Dubrovska G, Gollasch M. Palmitic acid methyl ester and its relation to control of tone of human visceral arteries and rat aortas by perivascular adipose tissue. Front Physiol. 2018;9:583.
  • 16. Mondéjar-Parreño G, Barreira B, Callejo M, et al. Uncovered contribution of kv7 channels to pulmonary vascular tone in pulmonary arterial hypertension. Hypertension. 2020;76:1134-46.
  • 17. Nurullahoğlu-Atalık KE, Kutlu S, Solak H, Özen-Koca R. Cilostazol enhances atorvastatin-induced vasodilation of female rat aorta during aging. Physiol Int. 2017;104:226–34.
  • 18. Sousa-Brito HL, Arruda-Barbosa L, Vasconcelos-Silva AA, et al. Vasorelaxant effect of trans-4-chloro-β-nitrostyrene, a synthetic nitroderivative, in rat thoracic aorta. Fundam Clin Pharmacol. 2021;35:331–40.
  • 19. Yang P, Read C, Kuc RE, et al. Elabela/toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system, and exogenous administration of the peptide compensates for the downregulation of its expression in pulmonary arterial hypertension. Circulation. 2017;135:1160-73.
  • 20. Perjés Á, Kilpiö T, Ulvila J, et al. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart. Basic Res Cardiol. 2016;111:2.
  • 21. Xu C. The Elabela in hypertension, cardiovascular disease, renal disease, and preeclampsia: an update. J Hypertens. 2021;39:12-22.
  • 22. Murza A, Sainsily X, Coquerel D, et al. Discovery and structure-activity relationship of a bioactive fragment of ELABELA that modulates vascular and cardiac functions. J Med Chem. 2016;59:2962-72.
  • 23. Ho L, van Dijk M, Chye STJ, et al. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. Science. 2017;357:707-13.
  • 24. Li Y, Yang X, Ouyang S, et al. Declined circulating Elabela levels in patients with essential hypertension and its association with impaired vascular function: a preliminary study. Clin Exp Hypertens. 2020;42:239-43.
  • 25. Wang Z, Yu D, Wang M, et al. Elabela-apelin receptor signaling pathway is functional in mammalian systems. Sci Rep. 2015;5:8170.
  • 26. Baranowska M, Kozłowska H, Korbut A, Malinowska B. Potassium channels in blood vessels: 10 their role in health and disease. Postepy Hig Med Dosw (Online). 2007;61:596-605.
  • 27. Cheng J, Wen J, Wang N, Wang C, Xu Q, Yang Y. Ion channels and vascular diseases. Arterioscler Thromb Vasc Biol. 2019;39:e146-56.
  • 28. Martelli A, Testai L, Breschi MC, et al. Vasorelaxation by hydrogen sulphide involves activation of Kv7 potassium channels. Pharmacol Res. 2013;70:27-34.
  • 29. Stott JB, Barrese V, Jepps TA, Leighton EV, Greenwood IA. Contribution of kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats. Hypertension. 2015;65:676-82.
  • 30. Jepps TA, Chadha PS, Davis AJ, Harhun MI, Cockerill GW, Olesen SP, et al. Downregulation of Kv7.4 channel activity in primary and secondary hypertension. Circulation. 2011;124:602-11
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Egzersiz Fizyolojisi, Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Serdar Şahintürk 0000-0002-7612-0055

Proje Numarası .
Yayımlanma Tarihi 27 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 45 Sayı: 5

Kaynak Göster

Vancouver Şahintürk S. Kv7.1-7.5 Kanallarının Sıçan Torasik Aortundaki Apela Kaynaklı Vasorelaksasyondaki Rolü. Osmangazi Tıp Dergisi. 2023;45(5):639-50.


13299        13308       13306       13305    13307  1330126978