The HMG-CoA reductase inhibitor cerivastatin enhances the nitric oxide bioavailability of the endothelium.
The aim of this study was to investigate whether the HMG-CoA reductase inhibitor cerivastatin alters the nitric oxide (NO) bioavailability of porcine aortic endothelial cell cultures and of native porcine coronary endothelium, after short-term (minutes) and long-term (24-hour) treatment with cerivastatin (electrochemical NO sensor). NO-synthase expression (Western blot, ELISA) and activity (3H-arginine assay) after cerivastatin treatment were determined. Furthermore, the authors investigated whether cerivastatin modulates an angiotensin II (10 micromol/L; 4 hours) induced reactive oxygen species (ROS) release from intact vessels (lucigenin-enhanced chemiluminescence-assay). Acute addition of cerivastatin induced a concentration-dependent NO release from endothelial cell cultures that could be blocked by the NO-synthase inhibitor N-monomethyl-arginine. A long-term incubation with cerivastatin also resulted in a concentration-dependent, significantly enhanced basal NO bioavailability (approximately 3-fold increase at 10 nmol/L cerivastatin) that could be partly reversed by a coincubation with mevalonate. No enhanced endothelial NO-synthase expression or increased NO-synthase activity was detected after long-term treatment with cerivastatin (24 hours). However, cerivastatin induced a significant concentration-dependent inhibition of the angiotensin II-induced ROS release from native endothelial cells of porcine coronary arteries. Therefore, there seems to be an acute and a long-term effect of cerivastatin that results in enhanced endothelial NO bioavailability.
Berkels
Reinhard
R
Institut fuer Pharmakologie, Universitaet zu Koeln, Germany. Reinhard.Berkels@medizin.uni-koeln.de
Nouri
Sepideh Khajeh
SK
Taubert
Dirk
D
Bartels
Henning
H
Roesen
Peter
P
Roesen
Renate
R
Klaus
Wolfgang
W
D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000493:pharmacokinetics*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C086276:cerivastatin; D019001:Nitric Oxide Synthase