Mechanism of impairment of NO production by aging and trials for the amelioration of endothelial function

衰老导致 NO 产生受损的机制以及改善内皮功能的试验

基本信息

批准号：
15590220
负责人：
KATANO Yumi
金额：
$ 1.92万
依托单位：
Yamagata University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590220/
关键词：
aging endothelila cell coronary circulation aorta red wine polyphenol NO PGI2 EDHF NOS発現量 COX発現量心筋冠血管 NO産生遊離量 PGI_2産生遊離量

项目摘要

The endothelial function is impaired by aging. Red wine polyphenol compounds (RWPCs) are suggested to have anti-atherosclerotic effect by scavenging oxygen-derived free radicals. In order to elucidate the acute effect of RWPCs, we examined the response of coronary flow in Langendorff-perfused rat heart and of aortic smooth muscle to RWPCs. We have shown that RWPCs increased coronary flow in vitro in aged rat as well as young rat. RWPCs relaxed the aortic vessels concentration-dependently in phenylephrine-precontracted smooth muscle preparations, both in young and aged rats. The vasorelaxant effecs were mediated by NO, PGI2 and EDHF in young rats, while by EDHF alone in aged rats. Next, we examined the cardiovascular effect of the RWPCs orally administered for a long term (up to 3 months). Rats were divided to three groups. Normal diet, high cholesterol diet, and high cholesterol plus RWPCs diet were given to each group, respectively. After 3 months, the vascular reactivity, platelet coagulability, and response of coronary flow were examined. The long term administration of RWPCs ameliorated the cardiovascular function. In cholesterol diet group, the platelet coagulation in response to ADP was dramatically increased, but the platelet dysfunction was improved by the addition of RWPCs into cholesterol diet. The endothelila function to release nitric oxide also tended to be better in the RWPCs group than that in cholesterol group. The importance of the arginine transporters which deliver arginine as a substrate of nitric oxide into endothelilal cells will be investigated in our future study to understand the mechanism of age-related cardiovascular disorders.

内皮功能因衰老而受损。红酒多酚化合物（RWPC）被认为通过清除氧自由基而具有抗动脉粥样硬化作用。为了阐明 RWPC 的急性作用，我们检查了 Langendorff 灌注大鼠心脏中的冠状动脉血流和主动脉平滑肌对 RWPC 的反应。我们已经证明，RWPC 在体外增加了老年大鼠和年轻大鼠的冠状动脉流量。在年轻和老年大鼠中，在去氧肾上腺素预收缩的平滑肌制剂中，RWPC 可以浓度依赖性地放松主动脉血管。在年轻大鼠中，血管舒张作用由 NO、PGI2 和 EDHF 介导，而在老年大鼠中，血管舒张作用仅由 EDHF 介导。接下来，我们检查了长期（长达 3 个月）口服 RWPC 的心血管效应。将大鼠分为三组。各组分别给予正常饮食、高胆固醇饮食、高胆固醇加RWPCs饮食。 3个月后，检查血管反应性、血小板凝固性和冠脉血流反应。长期服用 RWPC 可改善心血管功能。在胆固醇饮食组中，ADP引起的血小板凝固显着增加，但通过在胆固醇饮食中添加RWPC可以改善血小板功能障碍。 RWPCs 组的内皮细胞释放一氧化氮的功能也往往比胆固醇组更好。我们将在未来的研究中研究精氨酸转运蛋白的重要性，该转运蛋白将精氨酸作为一氧化氮的底物输送到内皮细胞中，以了解与年龄相关的心血管疾病的机制。