Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes
Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of Type 2 diabetes
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DOI：
10.1152/ajpheart.00229.2007
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发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Kamata, Katsuo
中科院分区：
文献类型：
--
作者：
Matsumoto, Takayuki;Kakami, Mika;Kamata, Katsuo
我们研究了老年大冢Long-Evans德岛肥胖（OLETF）大鼠（一种2型糖尿病模型）[与年龄匹配的对照组Long-Evans德岛大鼠（LETO）相比]的肠系动脉中内皮源性松弛因子（EDRFs）和内皮源性收缩因子（edcf）之间的平衡是否可能改变。在OLETF组中，乙酰胆碱诱导的弛豫受损，并且在高乙酰胆碱浓度下，两组均观察到弛豫逆转的趋势。这种倾向被吲哚美辛所消除。一氧化氮和/或内皮衍生的超极化因子介导的松弛以及磷酸化内皮一氧化氮合酶（Ser1177）和细胞外超氧化物歧化酶的蛋白表达也在OLETF中降低。在n - g -硝基- l -精氨酸（L-NNA）存在的情况下，乙酰胆碱诱导的收缩在较高的乙酰胆碱浓度下观察到，但在OLETF大鼠中更大。环氧化酶（COX）抑制剂和前列腺素受体拮抗剂可减少OLETF大鼠的这种收缩。在OLETF中，乙酰胆碱诱导的血栓素A(2)和PGE(2)的产生比LETO大鼠大，肠系膜动脉COX-1和COX-2蛋白的表达也比LETO大。此外，叔丁基过氧化氢（t-BOOH）（膜渗透氧化剂）诱导的浓度依赖性收缩在OLETF大鼠中更大。在LETO中，L-NNA和内皮去除均增加了t- boo介导的收缩，而在OLETF大鼠中没有，这表明内皮的负调节作用在OLETF大鼠中丧失了。这些结果表明，edrf和edcf之间的失衡可能与OLETF老年肠系膜动脉内皮功能障碍有关，并可能归因于氧化应激增加。
We investigated whether the balance between endothelium-derived relaxing factors (EDRFs) and endothelium-derived contracting factors (EDCFs) might be altered in mesenteric arteries from aged Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a Type 2 diabetic model) [vs. age-matched control Long-Evans Tokushima Otsuka (LETO) rats]. ACh-induced relaxation was impaired in the OLETF group, and a tendency for the relaxation to reverse at high ACh concentrations was observed in both groups. This tendency was abolished by indomethacin. Nitric oxide-and/or endothelium-derived hypolarizing factor-mediated relaxation and the protein expressions of phospho-endothelial nitric oxide synthase (Ser1177) and extracellular superoxide dismutase were also reduced in OLETF. An ACh-induced contraction was observed at higher ACh concentrations in the presence of N-G-nitro-L-arginine (L-NNA) but was greater in OLETF rats. This contraction in OLETF rats was reduced by cyclooxygenase (COX) inhibitors and by prostanoid-receptor antagonists. The ACh-induced productions of thromboxane A(2) and PGE(2) were greater in OLETF than LETO rats, as were the mesenteric artery COX-1 and COX-2 protein expressions. Moreover, tert-butyl hydroperoxide (t-BOOH) (membrane-permeant oxidant) induced a concentration-dependent contraction that was greater in OLETF rats. The t-BOOH-mediated contraction was increased both by L-NNA and by endothelium removal in LETO but not OLETF rats, suggesting that a negative modulatory role of the endothelium was lost in OLETF rats. These results suggest that an imbalance between EDRFs and EDCFs may be implicated in the endothelial dysfunction seen in aged OLETF mesenteric arteries, and may be attributable to increased oxidative stress.