Effects of fluvastatin on leukocyte-endothelial cell adhesion in hypercholesterolemic rats.
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 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 post-capillary venules by lipid mediators.
Kimura
M
M
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Kurose
I
I
Russell
J
J
Granger
D N
DN
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D007962:Leukocytes / Q000166:cytology; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D017035:Pravastatin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D000077340:Fluvastatin; D017035:Pravastatin