© 1997 American Heart Association, Inc.
Articles |
Effects of Fluvastatin on Leukocyte–Endothelial Cell Adhesion in Hypercholesterolemic Rats
From the Department of Physiology, Louisiana State University Medical Center, Shreveport.
Correspondence to D. Neil Granger, PhD, Department of Physiology and Biophysics, Louisiana State University Medical Center, 1501 Kings Hwy, PO Box 33932, Shreveport, LA 71130-3932. E-mail dgrang{at}lsumc.edu
Abstract The overall objective of this study was to determine whether peroral treatment with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin influences the leukocyte–endothelial cell adhesion (LECA) observed in postcapillary venules of hypercholesterolemic rats. Rats were fed either normal chow or a chow supplemented with 1% cholesterol for 10 days. Leukocyte adherence and extravasation, leukocyte rolling velocity, red blood cell velocity, and vessel diameter were monitored in mesenteric venules superfused with either 100 nmol/L platelet-activating factor (PAF) or 20 nmol/L leukotriene B4 (LTB4). Hypercholesterolemic rats exhibited an exaggerated LECA response compared with their normocholesterolemic counterparts. In hypercholesterolemic rats, treatment with fluvastatin significantly attenuated the leukocyte-adherence responses to PAF and LTB4 as well as the leukocyte emigration response to LTB4. Fluvastatin treatment also inhibited the PAF- and LTB4-induced reductions in leukocyte rolling velocity. These findings indicate that fluvastatin blunts the inflammatory responses elicited in postcapillary venules by lipid mediators.
Key Words: inflammation • postcapillary venules • atherosclerosis • leukocyte adherence
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