Pranidipine enhances the action of nitric oxide released from endothelial cells

Nitric oxide (NO) synthesis in vascular endothelium of patients:with hypert ension is altered. Calcium antagonists have been shown to improve endotheli al function in hypertensive patients, Here we report that pranidipine, one of the latest long-acting calcium antagonists in the dihydropyridine group, enhances the actions of NO released from endothelial cells (ECs). Pranidip ine significantly enhanced cGMP accumulation in vascular smooth muscle cell s cocultured with ECs, whereas amlodipine and nifedipine had no significant effects. In addition, pranidipine also suppressed basal and thrombin-stimu lated endothelin-1 production fi om ECs, Pranidipine also enhanced cGMP acc umulation in rat aortic segments with endothelium but not in endothelium-de nuded vessels. In contrast, pranidipine had no effect in the presence of N- G-monomethyl-L-arginine, an inhibitor of NO synthesis, Pranidipine did not affect the basal expression of endothelial NO synthase in ECs, However, pra nidipine upregulated the activity of superoxide dismutase in ECs, These fin dings suggest that pranidipine enhances NO action through inhibition of sup eroxide-induced NO decomposition in the vessel wall. Thus, pranidipine may be useful in the treatment of impaired endothelial function in patients wit h hypertension.