Celiprolol reduces the intimal thickening of autogenous vein grafts via an enhancement of nitric oxide function through an inhibition of superoxide production.
BACKGROUND
Beta-adrenoceptor antagonist celiprolol has been widely used as an effective antihypertensive agent. Some studies reported that celiprolol enhances nitric oxide production. The purpose of the present study is to examine the effects of celiprolol on vein graft intimal hyperplasia and endothelium-dependent nitric oxide (NO)-mediated relaxation.


METHODS
Japanese white rabbits were randomized to a control group that was fed regular rabbit chow or to a celiprolol group that was fed regular rabbit chow supplemented with 100 mg/body celiprolol sodium. The reversed jugular vein was implanted into the carotid artery. At 2 and 4 weeks after the operation, vein grafts in both groups were harvested, and intimal hyperplasia of the vein grafts was assessed. At 4 weeks after the operation, harvested vein grafts from both the groups were examined on the endothelium-dependent relaxation by application of Ach and were examined to detect for endothelial NO synthase (eNOS) expression and superoxide anion production.


RESULTS
Celiprolol inhibited intimal hyperplasia of carotid interposition-reversed jugular vein grafts 4 weeks after implantation (Intima/media index of celiprolol group, 0.48 +/- 0.01 vs control group, 1.07 +/- 0.08, P < .05) and suppressed cell proliferation in the neointima 2 weeks after implantation. In addition, celiprolol significantly enhanced endothelium-dependent NO-mediated relaxation in the vein graft with no change in eNOS expression and a reduction in superoxide production.


CONCLUSIONS
These novel findings clearly demonstrate that beta-adrenoceptor antagonist celiprolol can suppress intimal hyperplasia of the vein graft, which may be due to the enhancement of nitric oxide function through an inhibition of superoxide production. These results strongly support the clinical usefulness of celiprolol administration for preventing intimal hyperplasia of the vein graft after bypass grafting.
Hattori
Keisuke
K
Division of Vascular Surgery, Department of Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-chou, Showa-ku, Nagoya 466-8550, Japan.
Yamanouchi
Dai
D
Banno
Hiroshi
H
Kobayashi
Masayoshi
M
Yamamoto
Kiyoto
K
Kajikuri
Junko
J
Itoh
Takeo
T
Komori
Kimihiro
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000601:surgery*; D017272:Celiprolol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects*; D006965:Hyperplasia; D007601:Jugular Veins / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D008297:Male; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014182:Transplantation, Autologous; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014654:Vascular Patency / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D013481:Superoxides; D009569:Nitric Oxide; D017272:Celiprolol; D052250:Nitric Oxide Synthase Type III