Production of nitric oxide, but not prostacyclin, is reduced in klotho mice
Production of nitric oxide, but not prostacyclin, is reduced in klotho mice
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DOI：
10.1254/jjp.89.149
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发表时间：
2002-06-01
期刊：
影响因子：
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通讯作者：
Kurabayashi, M
中科院分区：
文献类型：
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作者：
Nakamura, T;Saito, Y;Kurabayashi, M
通过体内诱变建立了一种新的小鼠衰老模型（kl/kl小鼠）。我们分析了这种菌株的内皮功能。从6- 9周龄野生型（+/+）和杂合型（kl/+）klotho小鼠中获得胸主动脉环制备物。与+/+小鼠相比，kl/+小鼠的动脉对去甲肾上腺素的收缩反应增强，对乙酰胆碱和卵磷脂化超氧化物歧化酶（SOD）的血管舒张反应减弱。在kl/+小鼠中，对硝普钠的反应没有改变。用N-G-硝基-L-精氨酸甲酯（L-NAME，10（-5）M）处理后，+/+小鼠对去甲肾上腺素的收缩反应比kl/+小鼠更强。用L-NAME治疗取消了对乙酰胆碱和卵磷脂化SOD的血管舒张反应。与+/+小鼠相比，kl/+小鼠尿液中的NO代谢产物（NO2-和NO3-）和cGMP浓度显著降低。然而，6-酮-前列腺素F-1 α的尿排泄没有改变。在kl/+小鼠的主动脉中几乎没有NO合酶和血管内皮生长因子（VEGF）的免疫染色。在kl/kl小鼠的主动脉中未观察到NO合酶的免疫染色。klotho基因产物的表达可能在VEGF表达的调节中起作用，并且与NO的内皮释放紧密相关。
A novel murine model of aging (kl/kl mice) has been developed by in vivo mutagenesis. We analyzed endothelial function in this strain. Ring preparations of the thoracic aorta were obtained from 6- to 9-week old wild-type (+/+) and heterozygous (kl/+) klotho mice. The aortas of kl/+ mice showed an exaggerated contractile response to norepinephrine and attenuated vasodilator responses to acetylcholine and lecithinized superoxide dismutase (SOD) compared to +/+ mice. The response to sodium nitroprusside was unaltered in kl/+ mice. The contraction in response to norepinephrine was augmented by treatment with N-G-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) to a greater extent in +/+ mice than in kl/+ mice. Treatment with L-NAME abolished the vasodilator responses to both acetylcholine and lecithinized SOD. NO metabolites (NO2- and NO3-) and cGMP concentrations in the urine were significantly reduced in kl/+ mice compared to +/+ mice. However, the urinary excretion of 6-keto-prostaglandin F-1alpha was unaltered. There was little immunostaining for NO synthase and vascular endothelial growth factor (VEGF) in the aorta of kl/+ mice. No immunostaining for NO synthase was noted in the aorta of kl/kl mice. The expression of the klotho gene product may have a role in the regulation of VEGF expression and is tightly linked to endothelial release of NO.