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.


CONCLUSIONS
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.
Chen
H
H
Department of Cardiology, People's Hospital, Beijing University, Beijing 100044, China. chenhong@looksmart.com
Xing
Y
Y
Liu
R
R
D000818:Animals; D002478:Cells, Cultured; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052250:Nitric Oxide Synthase Type III; D017035:Pravastatin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D007375:Interleukin-1; D009569:Nitric Oxide; D000077340:Fluvastatin; D008148:Lovastatin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D017035:Pravastatin; D008798:Mevalonic Acid