Jpn. J. Pharmacol. 85 (2), 147-154 (2001)


Regulation of Endothelial Nitric Oxide Synthase and Endothelin-1 Expression by Fluvastatin in Human Vascular Endothelial Cells

Kazuyuki Ozaki1,*, Tadashi Yamamoto2, Takaharu Ishibashi3, Taku Matsubara1, Matomo Nishio3 and Yoshifusa Aizawa1

1First Department of Internal Medicine, 2Department of Renal Pathology, Institute of Nephrology, Niigata University School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan
3Department of Pharmacology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan
*Corresponding author. FAX: +81-25-227-0774
E-mail: k-ozaki@med.niigata-u.ac.jp


Abstract: 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 mM 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 mM fluvastatin for 12 h significantly reduced the production of endothelin-1 (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.

Keywords: Fluvastatin, 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, Nitric oxide, Endothelin-1, Endothelial cell

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