Flow-induced remodeling in resistance arteries from obese Zucker rats is associated with endothelial dysfunction
Flow-induced remodeling in resistance arteries from obese Zucker rats is associated with endothelial dysfunction
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DOI：
10.1161/hypertensionaha.107.088716
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发表时间：
2007-07-01
期刊：
影响因子：
8.3
通讯作者：
Henrion, Daniel
中科院分区：
文献类型：
--
作者：
Bouvet, Celine;de Chantemele, Eric Belin;Henrion, Daniel
血流的慢性增加增加了动脉直径和阻力动脉中的NO依赖性扩张。由于内皮功能障碍伴随着代谢综合征，我们假设肥胖大鼠阻力动脉中的血流介导的重塑可能受损。肥胖和瘦Zucker大鼠肠系膜阻力动脉暴露于慢性流量增加通过动脉结扎在体内：动脉暴露于高流量与正常流量的动脉进行了比较。使用压力动脉造影术在体外测量插管动脉的直径。7天后，在瘦的高流量动脉中发生向外重塑（在100 mm Hg下直径从346 +/-9增加到412 +/-11 μ m）.与瘦的动物相比，肥胖大鼠高流量动脉的内皮依赖性张力降低.另一方面，直径扩大发生在2株相似。肥胖大鼠中NO参与内皮依赖性扩张（通过NO阻断证实）和内皮NO合酶磷酸化的程度低于瘦大鼠。在肥胖大鼠中，超氧阴离子和还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚单位（p67 phox和gp 91 phox）表达增加，并且在高流量动脉中高于对照动脉。急性Tempol（过氧化氢酶模拟物）、过氧化氢酶加超氧化物歧化酶和L-精氨酸加四氢生物蝶呤使肥胖大鼠正常和高流量动脉的内皮依赖性扩张恢复到瘦对照动脉的水平。因此，肥胖阻力动脉中的血流诱导的重塑与内皮介导的舒张减少有关，因为NO生物利用度降低和过量的超氧化物产生。这种功能障碍可能对肥胖或代谢综合征患者的缺血性疾病产生负面影响。
Chronic increases in blood flow increase arterial diameter and NO-dependent dilation in resistance arteries. Because endothelial dysfunction accompanies metabolic syndrome, we hypothesized that flow- mediated remodeling might be impaired in obese rat resistance arteries. Obese and lean Zucker rat mesenteric resistance arteries were exposed to chronic flow increases through arterial ligation in vivo: arteries exposed to high flow were compared with normal flow arteries. Diameter was measured in vitro in cannulated arteries using pressure arteriography. After 7 days, outward remodeling ( diameter increased from 346 +/- 9 to 412 +/- 11 mu m at 100 mm Hg) occurred in lean high- flow arteries. Endothelium- dependent tone was reduced in high- flow arteries from obese rats by contrast with lean animals. On the other hand, diameter enlargement occurred similarly in the 2 strains. The involvement of NO in endothelium- dependent dilation ( evidenced by NO blockade) and endothelial NO synthase phosphorylation was smaller in obese than in lean rats. Superoxide anion and reduced nicotinamide- adenine dinucleotide phosphate oxidase subunit expression ( p67phox and gp91phox) increased in obese rats and were higher in high- flow than in control arteries. Acute Tempol ( a catalase mimetic), catalase plus superoxide dismutase, and L- arginine plus tetrahydrobiopterin restored endothelium- dependent dilation in obese rat normal and high- flow arteries to the level found in lean control arteries. Thus, flow- induced remodeling in obese resistance arteries was associated with a reduced endothelium- mediated dilation because of a decreased NO bioavailability and an excessive superoxide production. This dysfunction might have negative consequences in ischemic diseases in patients with obesity or metabolic syndrome.