Fluvastatin improves vascular functions in rabbit carotid arteries loaded with oxidative stress

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 N?-nitro L-arginine (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.