Pravastatin AMPK Yolağının ve Potasyum Kanallarının Aktivasyonu Yoluyla Sıçan Torasik Aortunu Gevşetir

Year 2024, Volume: 46 Issue: 1, 82 - 92, 16.01.2024

Serdar Şahintürk

https://doi.org/10.20515/otd.1285213

Abstract

Bu çalışma kolesterol düşürücü bir ilaç olan pravastatinin sıçan torasik aortundaki fonksiyonel etkilerini ve etki mekanizmalarını belirlemeyi amaçladı. Erkek Wistar Albino sıçanların torasik aortlarından izole edilen damar segmentleri, izole organ banyosu sistemindeki bölmelere yerleştirildi. Dinlenim gerimi 1 g olarak ayarlandı. Dengelenme sürecinden sonra torasik aorta halkaları 10-6 M fenilefrin ile kasıldı. Stabil bir kasılma sağlandıktan sonra damar halkalarına kümülatif (10-8-10-4 M) pravastatin uygulandı. Pravastatinin vazoaktif etki mekanizmalarını belirlemek için, belirtilen deney protokolü, spesifik sinyal yolağı inhibitörleri ve potasyum kanal blokörlerinin inkübasyonundan sonra tekrarlandı. Pravastatin, önceden kasılmış sıçan torasik aort halkalarında konsantrasyona bağımlı bir gevşeme gösterdi (p<0,001). Endotelin çıkarılması, L-NAME uygulaması ve indometazin inkübasyonu, pravastatinin vazorelaksan etki düzeyini anlamlı ölçüde azalttı (p<0,001). Pravastatin kaynaklı vazorelaksasyon seviyeleri, TEA, 4-Aminopiridin, XE-991, dorsomorfin ve anandamid uygulamalarından sonra anlamlı ölçüde azaldı (p<0,001). Gliburid ve baryum klorür uygulamaları pravastatinin vazorelaksan etki düzeyinde istatistiksel olarak anlamlı bir değişikliğe neden olmadı (p=1,000). Pravastatin sıçan torasik aortunda belirgin bir vazorelaksan etkiye sahiptir. Pravastatinin vazorelaksan etkisinde sağlam endotel, nitrik oksit, prostanoidler, AMPK ve potasyum kanalları (BKCa, SKCa, KV ve K2p kanalları) rol oynamaktadır.

Keywords

AMPK, Kolesterol, Nitrik oksit, Potasyum kanalları, Pravastatin, Sıçan aortu

Supporting Institution

Destek alınmamıştır.

Project Number

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Thanks

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Pravastatin Relaxes Rat Thoracic Aorta via Activation of AMPK Pathway and Potassium Channels

Abstract

This study aimed to determine the functional effects and mechanisms of action of pravastatin, a cholesterol-lowering drug, in rat thoracic aorta. Vessel segments isolated from the thoracic aortas of male Wistar Albino rats were placed in chambers within an isolated tissue bath system. The resting tension was set to 1 g. After an equilibration period, the thoracic aorta rings were contracted with 10-6 M phenylephrine. Once a steady contraction was obtained, cumulative pravastatin (10-8-10-4 M) was applied to the vascular rings. To identify the vasoactive effect mechanisms of pravastatin, the specified experimental protocol was repeated after incubation with specific signaling pathway inhibitors and potassium channel blockers. Pravastatin showed a concentration-dependent relaxation in precontracted rat thoracic aorta rings (p<0.001). The vascular relaxant effect levels of pravastatin were significantly reduced by removal of the endothelium, L-NAME application, and indomethacin incubation (p<0.001). Pravastatin-induced vasorelaxation levels were also significantly reduced following TEA, 4-Aminopyridine, XE-991, apamin, dorsomorphin, and anandamide administrations (p<0.001). However, applications of glyburide and barium chloride did not cause a statistically significant change in the vasorelaxant effect level of pravastatin (p=1.000). Pravastatin has a prominent vasorelaxant effect in rat thoracic aorta. Intact endothelium, nitric oxide, prostanoids, AMPK, and potassium channels (BKCa, SKCa, KV, and K2p channels) play a role in the vascular relaxant effect of pravastatin.

Keywords

AMPK, Cholesterol, Nitric oxide, Potassium channels, Pravastatin, Rat aorta

Project Number

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