Up-regulation of endothelial nitric oxide synthase through beta(2)-adrenergic receptor - The role of a beta-blocker with NO-releasing action

We determined the existence and role of beta (2)-adrenergic receptor in cul tured BAECs through the effect of a beta -blocker having NO releasing actio n; 3,4-dihydro-8 (2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzop yran; nipradilol on eNOS and eNOS regulatory protein caveolin-1. beta (2) r eceptor exists in BAECs. eNOS mRNA and protein were up-regulated by its tre atment whereas those of caveolin were not altered considerably. This eNOS u p-regulatory action was abolished by beta (2) receptor antagonist, ICI-1185 51. Increase of NO metabolites, protein and mRNA of eNOS was also partially inhibited by co-treatment of NOS inhibitor, L-NA with nipradilol. This is the first investigation of the action of non-selective beta blocker on eNOS through beta (2) receptor. The drug increases NO on incubation with BAECs about 50% as a NO donor and about 50% as results of eNOS up-regulation. (C) 2001 Academic Press.