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.

内皮功能会因衰老而损害。建议通过清除氧气衍生的自由基来具有抗动脉粥样硬化效应。为了阐明RWPC的急性效应，我们检查了Langendorff厌食大鼠心脏和主动脉平滑肌对RWPC中冠状动脉流动的反应。我们已经表明，RWPC在老年大鼠和年轻大鼠中增加了体外冠状动脉流动。 RWPC在年轻大鼠和年龄大鼠中，在苯丙烯 - 取消取消的平滑肌制剂中依赖于主动脉血管浓度。血管肌的效率是由年轻大鼠的NO，PGI2和EDHF介导的，而单独的EDHF则是老年大鼠的。接下来，我们检查了长期（长达3个月）口服的RWPC的心血管效应。大鼠分为三组。分别为每组提供正常饮食，高胆固醇饮食和高胆固醇加RWPCS饮食。 3个月后，检查了血管反应性，血小板凝结性和冠状动脉流动的反应。 RWPC的长期给药改善了心血管功能。在胆固醇饮食组中，响应ADP的血小板凝血大大增加，但是通过在胆固醇饮食中添加RWPC来改善血小板功能障碍。在RWPC组中，释放一氧化氮的内皮功能也比胆固醇组更好。在未来的研究中，将研究精氨酸转运蛋白将作为一氧化氮的底物作为一氧化氮的底物的重要性，以了解与年龄相关的心血管疾病的机制。