Benidipine treatment reduced neointimal area to 18,300 +/- 3,800 microm2 compared to 39,400 +/- 4,900 microm2 in vehicle-treated mice 4 weeks after carotid ligation.
Does benidipine prevent intimal thickening in mice with ligated carotid arteries?
Benidipine prevents intimal thickening and increases NO production in a mouse model of carotid artery ligation, suggesting a protective effect against vascular remodeling.
Absolute Event Rate: 18300% vs 39400%
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 +/- 4,900 microm2 (n = 8), whereas that in the drug-treated mice was reduced to 18,300 +/- 3,800 microm2 (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.
Yamashita et al. (Thu,) conducted a other in Vascular remodeling (n=18). Benidipine vs. Vehicle was evaluated on Neointimal area at 4 weeks after ligation. Benidipine treatment reduced neointimal area to 18,300 +/- 3,800 microm2 compared to 39,400 +/- 4,900 microm2 in vehicle-treated mice 4 weeks after carotid ligation.