Resistance of endothelium-dependent relaxation to elevation of O(-)(2) levels in rabbit carotid artery.
Resistance of endothelium-dependent relaxation to elevation of O(-)(2) levels in rabbit carotid artery.
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兔颈动脉内皮依赖性舒张对 O(-)(2) 水平升高的抵抗。
DOI：
10.1152/ajpheart.1999.277.5.h2109
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Cohen,RA
中科院分区：
文献类型：
--
作者：
Pagano,PJ;Griswold,MC;Najibi,S;Marklund,SL;Cohen,RA
内源性超氧阴离子干扰一氧化氮（NO）在内皮依赖性动脉舒张（EDR）中的生物活性。用光泽精化学发光法测定家兔胸、腹主动脉和颈动脉中NO的基础水平，以确定环境因素是否在三种动脉中存在差异，并有差别地减弱NO的作用。P< 0.05]，而ACh（10−8-10− 5 M）引起的EDR在ANOVA上无显著差异。在用超氧化物歧化酶（SOD）抑制剂二乙基二硫代氨基甲酸盐（DDC; 10 mM）治疗后，水平显著升高，在颈动脉和腹主动脉中变得比在胸主动脉中更高（185 ± 31.2和202 ± 40.3 vs. 89 ± 18 CU;P< 0.05）。DDC显著逆转胸主动脉的EDR，但不逆转颈动脉的EDR;在10− 6 M ACh时，DDC组胸主动脉和颈动脉的最大舒张分别减少48 ± 6.2%和6.8 ± 8.0%。在胸主动脉，外源性SOD可逆转DDC对EDR的抑制作用。此外，加入NO合成酶抑制剂硝基-l-精氨酸甲酯（300 μM;P< 0.05）可消除DDC/-抗性的颈动脉EDR，这与过氧亚硝酸盐或抗NO供体参与颈动脉舒张一致。事实上，外源性过氧亚硝酸盐引起的颈动脉和胸主动脉，这是不受DDC类似的松弛。我们的研究表明，颈动脉单位面积产生的亚硝酸盐和过氧亚硝酸盐的量更大，这表明它们的产物过氧亚硝酸盐的量更大。这些发现支持了过氧亚硝酸盐是颈动脉抗高血压的舒张剂的假设。
Endogenous superoxide anioninterferes with the bioactivity of nitric oxide (NO) in endothelium-dependent arterial relaxation (EDR). Using the lucigenin chemiluminescence assay, we measuredin the thoracic and abdominal aortas and the carotid artery of rabbits to determine whether ambientvaries among the three arteries and differentially diminishes the effect of NO. Basal levels ofwere significantly higher in carotid arteries than in the thoracic aorta [23 ± 6.1 vs. 3.9 ± 1.4 chemiluminescence units (CU);P< 0.05], whereas EDR in response to ACh (10−8–10−5M) was not significantly different on ANOVA. After treatment with the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DDC; 10 mM),levels were significantly elevated, becoming greater in the carotid artery and abdominal aorta than in the thoracic aorta (185 ± 31.2 and 202 ± 40.3 vs. 89 ± 18 CU;P< 0.05). DDC significantly reversed EDR in the thoracic aorta but not in the carotid artery; at 10−6M ACh, the decrease seen with DDC was 48 ± 6.2 vs. 6.8 ± 8.0% of maximal relaxation in the thoracic aorta and carotid artery, respectively. In the thoracic aorta, exogenous SOD reversed the inhibition of EDR caused by DDC. Moreover, DDC/-resistant EDR in the carotid artery was ablated by the addition of nitro-l-arginine methyl ester (300 μM;P< 0.05), an NO synthase inhibitor, consistent with peroxynitrite or an-resistant NO donor being involved in carotid relaxation. Indeed, exogenous peroxynitrite caused similar relaxation of the carotid artery and thoracic aorta, which was unaffected by DDC. Our studies show a greater production of nitrite andper unit area by the carotid artery, suggesting a greater amount of their product peroxynitrite. These findings support the hypothesis that peroxynitrite is the relaxing agent that resists highin the carotid artery.