Progression of coronary and mesenteric vascular dysfunction in Zucker obese and Zucker diabetic fatty rats
Progression of coronary and mesenteric vascular dysfunction in Zucker obese and Zucker diabetic fatty rats
复制标题
DOI：
10.1152/ajpheart.01297.2005
复制
发表时间：
2006-10-01
影响因子：
4.8
通讯作者：
Yorek, Mark A.
中科院分区：
文献类型：
--
作者：
Oltman, Christine L.;Richou, Laura L.;Yorek, Mark A.
我们研究了瘦型、Zucker肥胖型和Zucker糖尿病肥胖（ZDF）大鼠中与代谢综合征伴和不伴高血糖相关的血管功能障碍的进展。测量主动脉、小冠状动脉和肠系膜动脉对内皮依赖性和非依赖性血管扩张剂的反应。在整个研究过程中，ZDF大鼠血清中的氧化应激指数增加，而Zucker肥胖大鼠的数值在研究后期增加[硫代巴比妥酸反应物质：在28- 40周龄瘦、Zucker肥胖和ZDF大鼠的血清中分别为0.45 +/- 0.02、0.59 +/-0.03（P <0.05）和0.58 +/- 0.03（P < 0.05）μ g/ml]。乙酰胆碱（ACh）诱导的舒张血管从8-40周瘦动物没有改变。ACh诱导的舒张作用在28 - 36周龄Zucker肥胖大鼠的冠状动脉中几乎消失，在16-36周龄ZDF大鼠的冠状动脉中几乎消失，在ZDF大鼠的主动脉和肠系膜血管中减弱[10 μ M ACh的舒张%：72.2 +/- 7.1，17.9 +/- 5.9（P < 0.05），23.0 ± 4.5冠状动脉内（P < 0.05）;和67.9 +/- 9.2、50.1 +/- 5.5和42.3 +/- 4.7（P < 0.05）]。当血管与Tiron一起孵育时，ACh诱导的衰减舒张得到改善，表明超氧化物是内皮功能障碍的机制。硝普钠诱导的舒张在主动脉或冠状动脉中没有改变，在Zucker肥胖大鼠的肠系膜动脉中增强。我们的数据表明，糖尿病促进血管功能障碍的进展。氧化应激指数的增加先于功能障碍的发展，并可作为内皮损伤的标志。
We investigated the progression of vascular dysfunction associated with the metabolic syndrome with and without hyperglycemia in lean, Zucker obese, and Zucker diabetic fatty (ZDF) rats. Responses of aorta and small coronary and mesenteric arteries were measured to endothelium-dependent and -independent vasodilators. Indices of oxidative stress were increased in serum from ZDF rats throughout the study, whereas values were increased in Zucker obese rats later in the study [thiobarbituric acid reactive substances: 0.45 +/- 0.02, 0.59 +/- 0.03 (P < 0.05), and 0.58 +/- 0.03 (P < 0.05) mu g/ml in serum from 28- to 40-wk-old lean, Zucker obese, and ZDF rats, respectively]. Acetylcholine (ACh)-induced relaxation was not altered in vessels from lean animals from 8-40 wk. ACh-induced relaxation was nearly abolished in coronary arteries from 28 to 36-wk-old Zucker obese rats and by 16-36 wk in ZDF rats and was attenuated in aorta and mesenteric vessels from ZDF rats [%relaxation to 10 mu M ACh: 72.2 +/- 7.1, 17.9 +/- 5.9 (P < 0.05), and 23.0 +/- 4.5 (P < 0.05) in coronary vessels; and 67.9 +/- 9.2, 50.1 +/- 5.5, and 42.3 +/- 4.7 (P < 0.05) in mesenteric vessels from 28- to 40-wk-old lean, Zucker obese, and ZDF rats, respectively]. The attenuated ACh-induced relaxation was improved when vessels were incubated with tiron, suggesting superoxide as a mechanism of endothelial dysfunction. Sodium nitroprusside-induced relaxation was not altered in aorta or coronary arteries and was potentiated in mesenteric arteries from Zucker obese rats. Our data suggest that diabetes enhances the progression of vascular dysfunction. Increases in indices of oxidative stress precede the development of dysfunction and may serve as a marker of endothelial damage.