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

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.

Anahtar Kelimeler:

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

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

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.,

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