Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo.
The effect of a novel free radical scavenger, edaravone, on coronary endothelial dysfunction was examined in patients who had no significant stenosis of coronary arteries, to elucidate the role of free radicals on coronary endothelial dysfunction. The coronary blood flow (CBF) responses to acetylcholine (ACh) were measured by quantitative coronary arteriography and the intracoronary Doppler technique before and after the administration of edaravone. Twenty-four patients were divided into two groups on the basis of CBF responses to ACh; those with "attenuated" (%Delta CBF < 300%, n = 12) and "normal" (%Delta CBF > 300%, n = 12) flow responses. An intracoronary infusion of edaravone significantly improved ACh-induced increases in CBF in patients with attenuated flow responses; however, edaravone had no effect in those with normal flow responses (36.8% +/- 7.3% vs 0.0% +/- 5.1%, P < 0.01). The plasma levels of nitric oxide compounds (NOx) in the attenuated response group were lower than those in the normal group (35.7 +/- 2.3 vs 49.4 +/- 6.2 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.566, P < 0.01). The plasma level of malondialdehyde and 4-hydroxynonenal, which indicates the level of oxidative stress, in the attenuated group was higher than that in the normal group (6.9 +/- 0.9 vs 3.3 +/- 0.5 muM, P < 0.01) and correlated with the magnitude of CBF improvement by edaravone (r = 0.854, P < 0.01). A free radical scavenger improved the ACh-induced CBF response in patients with coronary atherosclerosis in vivo. Therefore, the current results suggest that scavenging free radicals has a beneficial effect for patients with coronary endothelial dysfunction.
Oyama
Jun-ichi
J
Department of Cardiovascular, Respiratory, and Geriatric Medicine, Kyushu University Hospital at Beppu and Medical Institute of Bioregulation, Kyushu University, Oita, Japan. joyama@tsurumi.beppu.kyushu-u.ac.jp
Satoh
Shinji
S
Suematsu
Nobuhiro
N
Kadokami
Toshiaki
T
Maeda
Toyoki
T
Sugano
Masahiro
M
Makino
Naoki
N
D000109:Acetylcholine / Q000008:administration & dosage; D000368:Aged; D000447:Aldehydes / Q000097:blood; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001783:Blood Flow Velocity / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015150:Echocardiography, Doppler; D000077553:Edaravone; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007548:Isosorbide Dinitrate / Q000008:administration & dosage; D007564:Japan; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
D000447:Aldehydes; D016166:Free Radical Scavengers; D005609:Free Radicals; D014665:Vasodilator Agents; D009569:Nitric Oxide; D008315:Malondialdehyde; D007548:Isosorbide Dinitrate; C027576:4-hydroxy-2-nonenal; D000109:Acetylcholine; D000077553:Edaravone; D000983:Antipyrine