A calcium channel blocker, benidipine, inhibits intimal thickening in the carotid artery of mice by increasing nitric oxide production

Objective Recent studies suggest that several calcium channel blockers exer t their protective effects against vascular disorders by increasing nitric oxide (NO) production from the endothelium, The purpose of this study was t o 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 ju st proximal to the carotid bifurcation. Treatment with benidipine (3 mg/kg per day) or vehicle was started 1 week before the carotid ligation, and con tinued throughout the experiments. Four weeks after the carotid ligation, t hese mice were killed and vascular remodeling was analyzed. Moreover, NO pr oduction and endothelial NO synthase (eNOS) expression were assessed. Results At 4 weeks after ligation, the neointimal area in the vehicle-treat ed mice was 39 400 +/- 4900 mum(2) (n = 8), whereas that in the drug-treate d mice was reduced to 18 300 +/- 3800 mum(2) (n = 10), Consequently, the lu minal area was 35% larger in the drug-treated mice. Benidipine increased th e basal as well as agonist-induced NO production from the endothelium, dete cted by Griess method or NOx analyzer. Endothelial NOS expression in vessel s of the drug-treated mice was increased compared with that of the vehicle- treated mice. Conclusion Our data provide evidence that benidipine increases NO productio n via increment of eNOS protein in vessels and prevents intimal thickening in mice. These results show the possibility of benidipine as a protective t ool against vascular remodeling independent of its effect on blood pressure . I Hypertens 19:451-458 (C) 2001 Lippincott Williams & Wilkins.