Osanai H, Okumura K, Hayakawa M, Harada M, Numaguchi Y, Mokuno S, Murase K, Matsui H, Toki Y, Ito T, Hayakawa T
Department of Internal Medicine II, Nagoya University School of Medicine, Japan.
J Cardiovasc Pharmacol. 2000 Dec;36(6):687-92. doi: 10.1097/00005344-200012000-00001.
This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.
(a) 在输注英脱利匹特（美国新泽西州皮帕克市法玛西亚-普强公司生产）前后，通过同步血管内二维超声和多普勒超声测量血管横截面积的变化，评估缺血后血管舒张情况；(b) 评估抗氧化剂抗坏血酸如何改变英脱利匹特对缺血后血管舒张的影响；(c) 阐明输注含或不含抗坏血酸的英脱利匹特后血浆亚硝酸盐和硝酸盐（NOx-）水平的变化。选用28只杂种犬，在动脉闭塞5分钟后测量髂动脉的血管横截面积和平均瞬时峰值速度。输注英脱利匹特（20%，2 ml/kg）后，缺血后血管舒张功能受损，而联合给予抗坏血酸（30 mg/kg）可逆转这种受损反应。NG-单甲基-L-精氨酸完全消除了缺血后血管舒张。与基线相比，输注英脱利匹特后血浆NOx水平显著降低（11.6±0.4对12.9±0.3 μM，p = 0.025），与基线相比，输注含抗坏血酸的英脱利匹特后血浆NOx水平也显著降低（11.8±0.5对13.1±0.4 μM，p = 0.047）。我们得出结论，抗坏血酸可逆转英脱利匹特诱导的内皮功能障碍，且不增加血浆NOx-水平，氧化应激导致的一氧化氮失活是英脱利匹特诱导的血管舒张受损的主要原因。
