科研之友
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摘要
Objective Recent studies suggest that several calcium channel blockers exert their protective effects against vascular disorders by increasing nitric oxide (NO) production from the endothelium, The purpose of this study was to clarify the effects of a long-lasting calcium channel blocker, benidipine, on vascular remodeling.
Methods The left common carotid arteries of mice were completely ligated just proximal to the carotid bifurcation. Treatment with benidipine (3 mg/kg per day) or vehicle was started 1 week before the carotid ligation, and continued throughout the experiments. Four weeks after the carotid ligation, these mice were killed and vascular remodeling was analyzed. Moreover, NO production and endothelial NO synthase (eNOS) expression were assessed.
Results At 4 weeks after ligation, the neointimal area in the vehicle-treated mice was 39 400 +/- 4900 mum(2) (n = 8), whereas that in the drug-treated mice was reduced to 18 300 +/- 3800 mum(2) (n = 10), Consequently, the luminal area was 35% larger in the drug-treated mice. Benidipine increased the basal as well as agonist-induced NO production from the endothelium, detected by Griess method or NOx analyzer. Endothelial NOS expression in vessels of the drug-treated mice was increased compared with that of the vehicle-treated mice.
Conclusion Our data provide evidence that benidipine increases NO production via increment of eNOS protein in vessels and prevents intimal thickening in mice. These results show the possibility of benidipine as a protective tool against vascular remodeling independent of its effect on blood pressure.
- 出版日期2001-3
