Chronic treatment with fluvastatin improves smooth muscle dilatory function in genetically determined hyperlipoproteinemia.
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.
Perings
Stefan Martin
SM
Department of Medicine, Division of Cardiology, Pulmonary Disease, and Angiology, Heinrich Heine University, Düsseldorf, Germany. perings@uni-duesseldorf.de
Grubert
Nike
N
Kleinbongard
Petra
P
Reinecke
Petra
P
Schulz
Rainer
R
Hermsen
Derik
D
Willers
Reinhart
R
Kelm
Malte
M
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
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009573:Nitrites; D000077340:Fluvastatin