Endojen apelin reseptör ligandlarının vasküler kontraktiliteye etkisi ve olası etki mekanizmalarının araştırılması
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Date
2021-03-26
Authors
Şahintürk, Serdar
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Apelinerjik sistem kardiyovasküler etkileri nedeniyle oldukça önemli olup, dünya çapında yaygın morbidite ve mortalite sebebi olan kardiyovasküler hastalıklarda yüksek tedavi potansiyeli taşımaktadır. Bu çalışmada apelinerjik sistem elemanları olan apelin ve elabelanın vasküler kontraktilite üzerindeki etkileri ve etki mekanizmaları araştırılmıştır. Erkek Wistar Albino sıçanların torasik aortlarından elde edilen damar halkaları izole organ banyosu sistemine yerleştirilmiştir. Dengelenme periyodu sonrasında fenilefrin ile kasılan damarlara plato fazında pyroglutamyl apelin-13 ([Pyr1]apelin-13) veya elabela-32 (Ela-32) kümülatif olarak uygulanarak damar gerimi üzerindeki etkileri incelenmiştir. Etki mekanizmalarını ortaya koymak amacı ile spesifik yolak inhibitörleri varlığında belirtilen protokol tekrarlanmıştır. Bu amaçla apelin reseptörü (APJ), endotelyal nitrik oksit sentaz (eNOS), AMP ile aktiflenen protein kinaz (AMPK), siklooksijenaz (COX), mitojenle aktiflenen protein kinaz (MAPK) ve potasyum kanal inhibitörleri kullanılmıştır. [Pyr1]apelin-13 fenilefrin ile ön kasılma uygulanmış sıçan torasik aortunda doz bağımlı olarak gevşemeye neden olmuştur. Ela-32 de benzer şekilde doz bağımlı vazodilatatör etki göstermiştir. Her iki etken maddenin de ortak reseptörleri olan APJ aracılığı ile vazodilatatör etki gösterdiği gözlenmiştir. [Pyr1]apelin-13’ün vazodilatatör etkisinde nitrik oksit (NO), AMPK, prostanoidler ve potasyum kanallarının rol oynadığı belirlenmiştir. Ela-32’nin vazodilatatör etkisine AMPK, prostanoidler ve potasyum kanallarının katıldığı gösterilmiştir. Ela-32’nin sıçan torasik aortundaki vazodilatatör etki düzeyinin [Pyr1]apelin-13’e kıyasla daha yüksek olduğu saptanmıştır. Sonuç olarak, bu çalışmada apelinerjik sistemin vazodilatatör etkinliğinde APJ, NO, AMPK, prostanoidler ve potasyum kanal aktivasyonunun rol oynadığı belirlenmiştir. Ela-32’nin [Pyr1]apelin-13’ten daha yüksek seviyede vazodilatasyona neden olduğu gösterilmiştir. Belirgin vazodilatatör etkileri nedeni ile apelinerjik sistem elemanlarının hipertansif hastalıklarda önemli bir tedavi alternatifi olabileceği düşünülmektedir.
The apelinergic system is very important due to its cardiovascular effects, and it has a high treatment potential in cardiovascular diseases, which are common causes of morbidity and mortality worldwide. In this study, the effects of apelin and elabela, which are the components of the apelinergic system, on vascular contractility and their mechanisms of action were investigated. Vascular rings obtained from the thoracic aorta of the male Wistar Albino rats were placed in an isolated organ bath system. After the equilibration period, pyroglutamyl apelin-13 ([Pyr1]apelin-13) or elabela-32 (Ela-32) was applied cumulatively to the vessels pre-contracted with phenylephrine in the plateau phase to investigate the effects on vascular tension. The protocol was repeated in the presence of specific pathway inhibitors to demonstrate their mechanism of action. For this purpose, apelin receptor (APJ), endothelial nitric oxide synthase (eNOS), AMPactivated protein kinase (AMPK), cyclooxygenase (COX), mitogen-activated protein kinase (MAPK), and potassium channel inhibitors were used. [Pyr1]apelin-13 induced a dose-dependent relaxation in the thoracic aorta of the rat pre-contracted with phenylephrine. Ela-32 also showed a dose-dependent vasodilator effect. It has been observed that both active ingredients act as a vasodilator through their common receptor, APJ. It has been determined that nitric oxide (NO), AMPK, prostanoids, and potassium channels play a role in the vasodilator effect of [Pyr1]apelin-13. It has been shown that AMPK, prostanoids, and potassium channels participate in the vasodilator effect of Ela-32. The vasodilator effect level of Ela-32 in rat thoracic aorta was found to be higher than [Pyr1]apelin-13. In conclusion, it was determined that APJ, NO, AMPK, prostanoids, and potassium channel activation play a role in the vasodilator activity of the apelinergic system. Ela-32 has been shown to cause a higher level of vasodilation than [Pyr1]apelin-13. It is thought that apelinergic system elements may be an important treatment alternative in hypertensive diseases due to their prominent vasodilator effects.
The apelinergic system is very important due to its cardiovascular effects, and it has a high treatment potential in cardiovascular diseases, which are common causes of morbidity and mortality worldwide. In this study, the effects of apelin and elabela, which are the components of the apelinergic system, on vascular contractility and their mechanisms of action were investigated. Vascular rings obtained from the thoracic aorta of the male Wistar Albino rats were placed in an isolated organ bath system. After the equilibration period, pyroglutamyl apelin-13 ([Pyr1]apelin-13) or elabela-32 (Ela-32) was applied cumulatively to the vessels pre-contracted with phenylephrine in the plateau phase to investigate the effects on vascular tension. The protocol was repeated in the presence of specific pathway inhibitors to demonstrate their mechanism of action. For this purpose, apelin receptor (APJ), endothelial nitric oxide synthase (eNOS), AMPactivated protein kinase (AMPK), cyclooxygenase (COX), mitogen-activated protein kinase (MAPK), and potassium channel inhibitors were used. [Pyr1]apelin-13 induced a dose-dependent relaxation in the thoracic aorta of the rat pre-contracted with phenylephrine. Ela-32 also showed a dose-dependent vasodilator effect. It has been observed that both active ingredients act as a vasodilator through their common receptor, APJ. It has been determined that nitric oxide (NO), AMPK, prostanoids, and potassium channels play a role in the vasodilator effect of [Pyr1]apelin-13. It has been shown that AMPK, prostanoids, and potassium channels participate in the vasodilator effect of Ela-32. The vasodilator effect level of Ela-32 in rat thoracic aorta was found to be higher than [Pyr1]apelin-13. In conclusion, it was determined that APJ, NO, AMPK, prostanoids, and potassium channel activation play a role in the vasodilator activity of the apelinergic system. Ela-32 has been shown to cause a higher level of vasodilation than [Pyr1]apelin-13. It is thought that apelinergic system elements may be an important treatment alternative in hypertensive diseases due to their prominent vasodilator effects.
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Keywords
Apelin, Elabela, NO, Potasyum kanalı, Vazodilatasyon, Potassium channel, Vasodilation
Citation
Şahintürk, S. (2021). Endojen apelin reseptör ligandlarının vasküler kontraktiliteye etkisi ve olası etki mekanizmalarının araştırılması. Yayınlanmamış doktora tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.