Lovastatin increases nitric oxide synthesis in IL- 1β- stimulated smooth muscle cells

Objective Nitric oxide (NO) production by inducible NO synthase (iNOS) may play an importa nt role in the pathogenesis of atherosclerosis. Although lovastatin has been s hown to reduce the progression of atherosclerosis, it is not known whether it re gulates NO production. We investigated the effects of lovastatin on NO synthesi s and the mechanisms by which lovastatin exerts its effects in rat vascular smoo th muscle cells. Methods Primary cultures of the vascular smooth muscle cells were obtained from the medi a of the thoracic aorta of Sprague Dawley rats (200-250 g). Nitrite levels in the culture medium of rat vascular smooth muscle cells were determined colorimet rically. Results Lovastatin (10(-5) mol/L) significantly increased interleukin- 1β (IL- 1β , 10 ng/mL)- induced nitrite accumulation in a time (0-24 hours)- dependent man ner. Exogenous mevalonate and geranylgeranyl- pyrophosphate completely reverse d the stimulatory effects of lovastatin on nitrite production. Furthermore, in hibition of Rho by C3 exoenzyme mimicked the increase in IL- 1β- induced nitrit e accumulation induced by lovastatin in the vascular smooth muscle cells. Conclusion These results demonstrate that lovastatin up- regulates NO formation in rat vasc ular smooth muscle cells stimulated by IL- 1β, and the effect may be associated with the inhibition of Rho activity.

Lovastatin increases nitric oxide synthesis in IL-1 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 lovastatin has been shown to reduce the progression of atherosclerosis, it is not known whether it regulates NO production. We investigated the effects of 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 were determined colorimetrically. RESULTS: Lovastatin (10(-5) mol/L) significantly increased interleukin-1 beta (IL-1 beta, 10 ng/mL)-induced nitrite accumulation in a time (0-24 hours)-dependent manner. Exogenous mevalonate and geranylgeranyl-pyrophosphate completely reversed the stimulatory effects of lovastatin on nitrite production. Furthermore, inhibition of Rho by C3 exoenzyme mimicked the increase in IL-1 beta-induced nitrite accumulation induced by lovastatin in the vascular smooth muscle cells. CONCLUSION: These results demonstrate that lovastatin up-regulates NO formation in rat vascular smooth muscle cells stimulated by IL-1 beta, and the effect may be associated with the inhibition of Rho activity.