Effects of Fluvastatin on Leukocyte-Endothelial Cell Adhesion in Hypercholesterolemic Rats

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 17; no. 8; pp. 1521 - 1526
• Main Authors: Kimura, Masaaki, Kurose, Iwao, Russell, Janice, Granger, D. Neil
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-08-1997; Hagerstown, MD Lippincott
• Subjects: Animals; Anticholesteremic Agents - pharmacology; Biological and medical sciences; Cell Adhesion - drug effects; Cell Movement - drug effects; Cholesterol, Dietary - administration & dosage; Endothelium, Vascular - cytology; Enzyme Inhibitors - therapeutic use; Fatty Acids, Monounsaturated - therapeutic use; Fluvastatin; General and cellular metabolism. Vitamins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia - drug therapy; Indoles - therapeutic use; Leukocytes - cytology; Leukotriene B4 - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Platelet Activating Factor - pharmacology; Pravastatin - pharmacology; Rats; Rats, Sprague-Dawley; Endothelial cell; Rat; Rodentia; Oral administration; Metabolic diseases; Exploration; Lipids; Hyperlipoproteinemia; Venule; Adhesion; Biological activity; Chemotherapy; Vertebrata; Mammalia; Treatment; Fluvastatin; Hypercholesterolemia; Animal; Dyslipemia; Antilipemic agent
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.17.8.1521

The overall objective of this study was to determine whether peroral treatment with the 3-hydroxy-3-methyl-glutaryl 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 LTB (4) 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 post-capillary venules by lipid mediators. (Arterioscler Thromb Vasc Biol. 1997;17:1521-1526.)