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 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.
Jayachandran
M
M
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Hayashi
T
T
Sumi
D
D
Thakur
N K
NK
Kano
H
H
Ignarro
L J
LJ
Iguchi
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D051242:Caveolin 1; D022461:Caveolins; D020030:Nitric Oxide Donors; D011412:Propanolamines; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D019335:Nitroarginine; D009569:Nitric Oxide; C026777:ICI 118551; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C036089:nipradilol