Inhibitory effect of fluvastatin at doses insufficient to lower serum lipids on the catheter-induced thickening of intima in rabbit femoral artery.
The anti-atherosclerotic effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors at doses insufficient to lower serum cholesterol was investigated in rabbit femoral artery denuded by balloon catheter. Fluvastatin and pravastatin were given orally at doses of 4 and 8 mg/kg per day, respectively, for 2 weeks after the catheterization. There was little change in serum cholesterol, triglyceride and phospholipid by chronic treatment with the drugs. The cross-sectional area of the intima, expressed as relative values to media (I/M ratio), was increased by the catheterization, showing intimal thickening in the denuded arteries. The I/M ratio was reduced by fluvastatin but not pravastatin: 0.327 +/- 0.060 for control, 0.116 +/- 0.035 for 4 mg/kg fluvastatin, 0.088 +/- 0.027 for 8 mg/kg fluvastatin and 0.22 +/- 0.069 for 8 mg/kg pravastatin. Fluvastatin (8 mg/kg)-induced effect on the I/M ratio, was prevented by the combined administration with 40 mg/kg per day mevalonate, a metabolite in the HMG-CoA reductase pathway. These results suggest that fluvastatin inhibits intimal thickening after catheterization-induced injury through percutaneous transluminal coronary angioplasty (PTCA) and that the inhibition is presumably attributed to reduced migration and proliferation of smooth muscle cells but not secondarily to a lowering of serum lipid.
Bandoh
T
T
Department of Pharmacology, Sandoz Tsukuba Research Institute, Ibaraki, Japan.
Mitani
H
H
Niihashi
M
M
Kusumi
Y
Y
Ishikawa
J
J
Kimura
M
M
Totsuka
T
T
Sakurai
I
I
Hayashi
S
S
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002404:Catheterization; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005263:Femoral Artery / Q000187:drug effects* / Q000473:pathology; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006965:Hyperplasia / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin / Q000627:therapeutic use; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; D000077340:Fluvastatin; D002784:Cholesterol; D017035:Pravastatin; D008798:Mevalonic Acid