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FLUVASTATIN IMPROVES VASCULAR FUNCTIONS IN RABBIT CAROTID ARTERIES LOADED WITH OXIDATIVE STRESS

Journal Name:

  • Ankara Üniversitesi Eczacılık Fakültesi Dergisi

Publication Year:

  • 2007

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Oxidative stress is implicated in most cardiovascular diseases and reactive oxygen species (ROS) have a major role in vascular endothelial cell signal transduction. 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitors including fluvastatin do not only lower plasma cholesterol but also have non-cholesterol lowering (direct) effects on the vessel wall which decrease cardiovascular complications. The effects of fluvastatin are investigated in isolated rabbit carotid artery subjacent diethyldithiocarbamic acid (DETCA)-generated oxidative stress and in relation to nitric oxide synthase inhibition by Nω-nitro Larginine (L-NA) on responses. Four arterial segments were used from each rabbit. The rings were subjected to reactive oxygen species by incubation with DETCA (3mM) for 30 minutes. Fluvastatin was added to bath 10 minutes before DETCA incubation. L-NA (10-4M) was used in one of the organ bath. The relaxant response to acetylcholine (ACh) and contractile reponses to phenylephrine (PE) and serotonin (5HT) were determined. Contractility and sensitivity to serotonin in vessels were not affected by DETCA. Treatment with DETCA diminished the maximum relaxation and sensitivity to ACh. These effects were prevented by fluvastatin. Incubation with L-NA reversed the increased ACh-relaxation induced by fluvastatin. Maximum contractile responses and sensitivity to PE were attenuated in DETCA-treated rings. Fluvastatin normalized the decreased PE contractility caused by DETCA. In conclusion, fluvastatin improves vascular functions under oxidative stress independent of lipid lowering in isolated carotid artery.
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Abstract (Original Language): 
Oksidatif stres kardiyovasküler hastalıkların pek çoğuyla ilişkilidir ve reaktif oksijen türleri (ROS) damar endotel hücrelerinin sinyal transdüksiyonunda önemli bir role sahiptir. Fluvastatinin dahil olduğu 3- hidroksi-3 metil koenzim A (HMG-CoA) redüktaz inhibitörleri sadece plazma kolesterolünü düşürmekle kalmaz aynı zamanda da damar duvarı üzerinde kardiyovasküler komplikasyonları azaltan kolesterol düşürücü etkiden bağımsız direkt etkilere de sahiptir. Fluvastatinin dietiltiyokarbamik asit (DETCA) ile oluşturulan oksidatif strese maruz kalmış izole tavşan karotid arterindeki etkileri ve yanıtlar üzerinde Nω- nitro L-arjinin (L-NA) ile nitrik oksit inhibisyonun ilişkisi araştırılmıştır. Her bir tavşandan dört arter segmenti kullanıldı. Ringler, 3mM DETCA ile 30 dakika inkübe edilmek suretiyle reaktif oksijen türlerine maruz bırakıldılar. Fluvastatin, DETCA inkübasyonundan 10 dakika önce banyoya ilave edildi. Organ banyosunun birinde 10-4M L-NA kullanıldı. Asetilkoline (ACh) karşı gevşeme yanıtları ile fenilefrin (PE) ve serotonine (5-HT) kasılma yanıtları araştırıldı. Damarlarda serotonine karşı kasılmalar ve duyarlılık DETCA’dan etkilenmedi. DETCA ile tedavi ACh gevşemeleri ve duyarlığı azalttı. Bu etkiler fluvastatin ile engellendi. L-NA ile inkübasyon fluvastatin tarafından oluşturulan ACh gevşemelerindeki artışı geriye döndürdü. DETCA tedavisi gören ringlerde PE maksimum kasılma yanıtları ve duyarlığı azaldı. Fluvastatin DETCA’nın neden olduğu PE kasılma yanıtlarındaki azalmayı normalize etti. Sonuç olarak, fluvastatin izole karotid arterinde oksidatif stres altında bozulan damar fonksiyonlarını lipid düşürücü etkisinden bağımsız olarak iyileştirmektedir.
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