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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.

内皮功能随着年龄的增长而受损。红酒多酚类化合物（RWPCs）可能通过清除氧自由基而发挥抗动脉粥样硬化作用。为了阐明RWPCs的急性效应，我们研究了Langendorff灌注大鼠心脏和主动脉平滑肌对RWPCs的冠状动脉血流的反应。我们已经表明，RWPCs增加冠状动脉流量在体外老年大鼠以及年轻大鼠。RWPCs放松主动脉血管浓度依赖性苯肾上腺素预收缩平滑肌制剂，无论是在年轻和老年大鼠。在青年大鼠中，NO、PGI2和EDHF共同发挥舒张血管的作用，而在老年大鼠中，EDHF单独发挥舒张血管的作用。接下来，我们检查了长期口服RWPC（长达3个月）的心血管效应。将大鼠分为三组。各组分别给予普通饲料、高胆固醇饲料、高胆固醇加RWPC饲料。3个月后，检测血管反应性、血小板凝固性和冠状动脉血流反应性。长期服用RWPC可改善心血管功能。胆固醇饲料组ADP诱导的血小板凝血功能明显增强，而胆固醇饲料中添加RWPCs可改善血小板功能障碍。RWPCs组内皮细胞释放一氧化氮的功能也有优于胆固醇组的趋势。精氨酸转运蛋白作为一氧化氮的底物将精氨酸转运到内皮细胞，其重要性将在我们未来的研究中进行研究，以了解年龄相关的心血管疾病的机制。