Rosuvastatin relaxes rat thoracic aorta, pulmonary artery, and trachea via nitric oxide, prostanoids, and potassium channels

Year 2023, Volume: 48 Issue: 2, 419 - 431, 02.07.2023

Serdar Şahintürk

https://doi.org/10.17826/cumj.1279122

Cited By: 1

Abstract

Purpose: This study aimed to determine the functional effects and mechanisms of the action of rosuvastatin on vascular and tracheal smooth muscle tissues.
Materials and Methods: Vascular and tracheal rings (2-3 mm) isolated from the thoracic aortas, pulmonary arteries, and tracheas of Wistar Albino male rats (250-300 g) were placed in chambers in the isolated tissue bath system. As the resting tension, 1 g was selected. Vascular rings contracted with 10-6 M phenylephrine after a 90-minute equilibration period. Tracheal rings contracted with 10-5 M acetylcholine. After the contraction was steady, rosuvastatin (10-8-10-4 M) was cumulatively applied to the vascular and tracheal rings. The defined experimental methodology was repeated following the incubation of selective inhibitors of signaling pathways and K+ channel blockers to ascertain rosuvastatin's functional effect mechanisms.
Results: In the precontracted rat vascular and tracheal rings, rosuvastatin induced concentration-dependent relaxation. The maximal relaxation level in vessel samples was 96%. On the other hand, the maximal relaxation level in tracheal samples was found to be 75%. The vasorelaxant effects of rosuvastatin were dramatically attenuated by endothelium removal, L-NAME treatment, and indomethacin incubation (up to 27%). With the incubation of tetraethylammonium, glyburide, 4-Aminopyridine, and anandamide, rosuvastatin-mediated vascular smooth muscle relaxation levels were significantly decreased (up to 38%). Moreover, With the incubation of tetraethylammonium, glyburide, and 4-Aminopyridine rosuvastatin-mediated tracheal smooth muscle relaxation levels were significantly decreased (up to 30%).
Conclusion: Rosuvastatin has a noticeable relaxing effect on the vascular and tracheal smooth muscles. The vasorelaxant effect of rosuvastatin involves intact endothelium, nitric oxide, prostanoids, and K+ channels (BKCa, KV, and KATP channels). Furthermore, nitric oxide, prostanoids, BKCa channels, KV channels, and KATP channels play a role in rosuvastatin-induced tracheal smooth muscle relaxation

Keywords

Aorta, nitric oxide, potassium, pulmonary artery, rosuvastatin, trachea.

Supporting Institution

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Project Number

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Thanks

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Rosuvastatin, sıçan torasik aortunu, pulmoner arterini ve trakesini nitrik oksit, prostanoidler ve potasyum kanalları yoluyla gevşetir

Abstract

Amaç: Bu çalışma rosuvastatin'in vasküler ve trakeal düz kas dokuları üzerindeki işlevsel etkilerini ve etki mekanizmalarını belirlemeyi amaçladı.
Gereç ve Yöntem: Wistar Albino erkek sıçanların (250-300 g) torasik aortları, pulmoner arterleri ve trakealarından izole edilen vasküler ve trakeal halkalar (2-3 mm), izole doku banyosu sistemindeki haznelere yerleştirildi. Dinlenme gerimi olarak 1 g seçildi. Vasküler halkalar, 90 dakikalık dengeleme periyodundan sonra 10-6 M fenilefrin ile kasıldı. Trakeal halkalar ise 10-5 M asetilkolin ile kasıldı. Kasılma stabil hale geldikten sonra, rosuvastatin (10-8-10-4 M) vasküler ve trakeal halkalara kümülatif olarak uygulandı. Rosuvastatin'in işlevsel etki mekanizmalarını belirlemek için seçici sinyal yolak inhibitörleri ve K+ kanal blokerlerinin inkübasyonu sonrasında belirlenen deneysel metodoloji tekrar edildi.
Bulgular: Rosuvastatin, ön kasılma uygulanmış sıçan vasküler ve trakeal halkalarında doz bağımlı bir gevşeme oluşturdu. Damar örneklerindeki maksimal gevşeme düzeyi % 96 idi. Öte yandan, trake örneklerindeki maksimal gevşeme düzeyi % 75 olarak bulundu. Rosuvastatin'in vazodilatör etkileri, endotelin çıkarılması, L-NAME tedavisi ve indometazin inkübasyonu ile anlamlı olarak azaldı (% 27’ye kadar). Tetraethylammonium, gliburid, ve 4-Aminopiridin inkübasyonu ile rosuvastatin kaynaklı vasküler düz kas gevşeme düzeyleri önemli ölçüde azaldı (% 38’e kadar). Dahası, tetraethylammonium, gliburid ve 4-Aminopiridin inkübasyonu ile rosuvastatin ile uyarılan trakeal düz kas gevşeme düzeyleri anlamlı olarak azaldı (% 30’a kadar).
Sonuç: Rosuvastatinin vasküler ve trakeal düz kaslarda belirgin bir gevşetici etkisi vardır. Rosuvastatin'in vazodilatör etkisi, sağlam endotel, nitrik oksit, prostanoidler ve K+ kanalları (BKCa, KV ve KATP kanalları) ile ilişkilidir. Ayrıca, nitrik oksit, prostanoidler, BKCa kanalları, KV kanalları ve KATP kanalları, rosuvastatin tarafından indüklenen trakeal düz kas gevşemesinde rol oynamaktadır.

Keywords

Aort, nitrik oksit, potasyum, pulmoner arter, rosuvastatin, trake.

Project Number

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