Regulation of endothelial nitric oxide synthase and endothelin-1 expression by fluvastatin in human vascular endothelial cells

We investigated the effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on endothelial vasoactive substances using human umbilical vein endothelial cells (HUVECs). Incubation of HUVECs with fluvastatin for 12 h increased endothelial nitric oxide synthase (eNOS) mRNA expression in a concentration-dependent manner (peak, 276 +/- 38%, mean +/- S.D., of the control, at 1.0 muM fluvastatin, P<0.01). In addition, fluvastatin increased eNOS protein production (245 +/- 51% of the control level, P<0.05) as well as nitrite production (165 +/- 35% of the control level, P<0.01). In contrast, incubation of HUVECs with 1.0 <mu>M fluvastatin for 12 h significantly reduced the production of endothelin-l (ET-1) and preproET-1 mRNA expression in HUVECs (28 +/- 1% and 39 +/- 1% of the control level, respectively, P<0.01). Our results suggest that fluvastatin might be involved in improvement of' endothelial function and prevention of the progression of atherosclerosis.