Lovastatin increases nitric oxide synthesis in IL-I beta- stimulated smooth muscle cells

Objective Nitric oxide (NO) production by inducible NO synthase (iNOS) may play an important role in the pathogenesis of atherosclerosis. Although lov astatin has been shown to reduce the progression of atherosclerosis, it is not known whether it regulates NO production. We investigated the effects o f lovastatin on NO synthesis and the mechanisms by which lovastatin exerts its effects in rat vascular smooth muscle cells. Methods Primary cultures of the vascular smooth muscle cells were obtained from the media of the thoracic aorta of Sprague Dawley rats (200 - 250 g). Nitrite levels in the culture medium of rat vascular smooth muscle cells we re determined colorimetrically. Results Lovastatin (10(-5) mol/L) significantly increased interleukin-1 bet a (IL-1 beta, 10 ng/mL)-induced nitrite accumulation in a time (0 - 24 hour s)-dependent manner, Exogenous mevalonate and geranylgeranyl-pyrophosphate completely reversed the stimulatory effects of lovastatin on nitrite produc tion. Furthermore, inhibition of Rho by C3 exoenzyme mimicked the increase in IL-1 beta -induced nitrite accumulation induced by lovastatin in the vas cular smooth muscle cells. Conclusion These results demonstrate that lovastatin up-regulates NO format ion in rat vascular smooth muscle cells stimulated by IL-1 beta, and the ef fect may be associated with the inhibition of Rho activity.