The HMG-CoA reductase inhibitor cerivastatin enhances the nitric oxide bioavailability of the endothelium.

Abstract:

: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.

journal_name

J Cardiovasc Pharmacol

authors

Berkels R,Nouri SK,Taubert D,Bartels H,Roesen P,Roesen R,Klaus W

doi

10.1097/00005344-200309000-00006

subject

Has Abstract

pub_date

2003-09-01 00:00:00

pages

356-63

issue

3

eissn

0160-2446

issn

1533-4023

journal_volume

42

pub_type

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