title: Chronic treatment with fluvastatin improves smooth muscle dilatory function in genetically determined hyperlipoproteinemia.
abstract: We hypothesized that the HMG-CoA reductase inhibitor fluvastatin, does not only improve endothelium-dependent vasorelaxation, but that it also increases vascular smooth muscle reactivity in hyperlipoproteinemia. New Zealand White (NZW) rabbits aged 37 weeks (control), Watanabe Heritable Hyperlipidemic rabbits (WHHL) aged 37 weeks, and WHHL aged 35 weeks with fluvastatin treatment of 17 weeks (10 mg/kg/d) were examined. Aortas were isolated for isometric tension recording. Both endothelium-dependent and independent relaxation were impaired in WHHL. Fluvastatin significantly restored impaired endothelium-independent relaxation (WHHL: 57 +/- 12 versus WHHL+ fluvastatin: 150 +/- 22%; P < 0.05) and in tendency endothelium-dependent relaxation (WHHL: 26 +/- 5 versus WHHL+ fluvastatin: 83 +/- 29%; (P = 0.07)). In parallel, fluvastatin restored nitrite plasma level in hyperlipoproteinemic animals (WHHL: 480 (13-3821) versus WHHL+ fluvastatin: 808 (467-1595) nmol; P < 0.05). Thus, chronic treatment with fluvastatin not only improves endothelial but also vascular smooth muscle function in hyperlipoproteinemia, which may contribute to the beneficial clinical effects of statins.
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonary Disease, and Angiology, Heinrich Heine University, Düsseldorf, Germany. perings@uni-duesseldorf.de
authors.forename: Stefan Martin
authors.initials: SM
authors.lastname: Perings
authors.forename: Nike
authors.initials: N
authors.lastname: Grubert
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Petra
authors.initials: P
authors.lastname: Reinecke
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Derik
authors.initials: D
authors.lastname: Hermsen
authors.forename: Reinhart
authors.initials: R
authors.lastname: Willers
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000818:Animals; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006951:Hyperlipoproteinemias / Q000188:drug therapy* / Q000235:genetics; D007211:Indoles / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D011817:Rabbits
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009573:Nitrites; D000077340:Fluvastatin