Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo
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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” (%Δ CBF < 300%, n = 12) and “normal” (%Δ 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 μM, 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 μM, 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.
Key wordsFree radical Endothelial dysfunction Coronary atherosclerosis
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- 9.Cai H, Harrison D (2001) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress, Circ Res 87:840–844Google Scholar
- 15.Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, Kiowski W, Luscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:233–246CrossRefPubMedGoogle Scholar
- 16.Hoeschen RJ (1997) Oxidative stress and cardiovascular disease. Can J Cardiol 11:1021–1025Google Scholar
- 24.Yamazaki K, Miwa S, Toyokuni S, Nemoto S, Oriyanhan W, Takaba K, Saji Y, Marui A, Nishina T, Ikeda T, Komeda M (2009) Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart. Heart Vessels 24:228–235CrossRefPubMedGoogle Scholar
- 29.Yamamoto Y, Kuwahara T, Watanabe K, Watanabe K (1996) Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one. Redox Rep 2:333–338Google Scholar
- 34.Yoshida H, Sasaki K, Namiki Y, Sato N, Tada N (2005) Edaravone, a novel radical scavenger, inhibits oxidative modification of lowdensity lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase. Atherosclerosis 179:97–102CrossRefPubMedGoogle Scholar