In vitro antioxidant activity of pravastatin provides vascular protection.
The production of reactive oxygen species plays roles during the development of endothelial dysfunction and it represents a significant prognostic factor for evaluating the risk of cardiovascular disease. Although statins target cholesterol biosynthesis, the beneficial effects on cardiovascular disease remain to be fully elucidated. In this work, we explored the in vitro effects of pravastatin on vascular functionality. We studied the effect of the incubation with this statin on acetylcholine relaxation using aorta from spontaneously hypertensive rats (SHR). Consistent with a cholesterol-independent mechanism of action, we show that pravastatin induces a significant improvement of endothelium-dependent relaxation that is not completely reversed by mevalonic acid. Assays with 250microM of lucigenin were carried out to verify whether such action could be mediated by the scavenger properties of pravastatin. Treatment of aortic rings derived from Wistar rats with lucigenin promotes superoxide generation (O(2)(-)) and the subsequent loss of both endothelium-dependent and independent relaxations. The addition of pravastatin reduced the lucigenin-triggered O(2)(-) levels as well as its inhibitory effects on acetylcholine- and sodium nitroprusside-dependent responses. These effects were not counteracted by mevalonic acid, further supporting the idea that the effects of pravastatin do not entail alterations in cholesterol biosynthesis. In conclusion, this study can contribute to elucidate the mechanism responsible for the antioxidant activity of pravastatin, and describes relationship between a scavenger effect of pravastatin and the improvement of vascular reactivity.
Kassan
Modar
M
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Montero
María José
MJ
Sevilla
María Angeles
MA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013997:Time Factors
D000975:Antioxidants; D017035:Pravastatin