Atorvastatin improves function of vascular endothelium by decreasing oxidative stress

Abstract

Vascular oxidative injury is involved in numerous cardiovascular diseases, particularly in hypertension and atherosclerosis. Statins ‐‐ a family of lipid lowering drugs ‐‐ appear to display non‐lipid modifying abilities. The aim of this study was to investigate the effect of atorvastatin on vascular tone and its vasoprotection against oxidative stress injury. The tension of the isolated rat thoracic aortic rings was measured using organ bath technique and superoxide arterial injury was induced by pyrogallol (which produces superoxide anions) incubation. We found that atorvastatin (10−7 M ‐ 10−4 M) caused a concentration‐dependent relaxation in endothelium‐intact aortic rings precontracted by phenylephrine (PE, 10−6 M), which was abolished by L‐NAME (10−4 M), a nitric oxide synthase inhibitor. However, atorvastatin did not relax endothelium‐denuded aortic rings. Exposure to pyrogallol (3 ?10−4 M) for 15 min inhibited the acetylcholine (ACh, 10−9 M ‐ 10−5 M)‐induced relaxation in aortic rings precontracted by PE. This superoxide anion‐induced impairment was attenuated by pre‐incubation of atorvastatin (10−5 M) for 30 min. Atorvastatin administration (2, 10, 50 mg·kg−1·d−1, respectively) by gavage for 14 days did not alter the body weight of the rats, but showed improvement of ACh‐induced relaxation in aortic rings exposure to pyrogallol. These results indicate that atorvastatin has an endothelium‐dependent vasodilating effect on rat aorta, mediated by nitric oxide. Both acute and chronic administration of atorvastatin protect aorta from oxidative stress injury.