Up-regulation of endothelial nitric oxide synthase through β2-adrenergic receptor -: The role of a β-blocker with NO-releasing action

We determined the existence and role of beta (2)-adrenergic receptor in cultured BAECs through the effect of a beta -blocker having NO releasing action; 3,4-dihydro-8 (2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran; nipradilol on eNOS and eNOS regulatory protein caveolin-1. beta (2) receptor exists in BAECs. eNOS mRNA and protein were up-regulated by its treatment whereas those of caveolin were not altered considerably. This eNOS up-regulatory action was abolished by beta (2) receptor antagonist, ICI-118551. 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.