THE MECHANISM OF AGE-RELATED CHANGES IN THE RELEASE OF NITRIC OXIDE.

一氧化氮释放与年龄相关的变化机制。

基本信息

批准号：
11670658
负责人：
KATANO Yumi
金额：
$ 2.3万
依托单位：
YAMAGATA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The incidence of cardiovascular disorder due to coronary artery disease increases with advansing age. Endothelium plays an important role in regulating vascular tone and in maintaining the cardiovascular function. We previously demonstrated that several vasoconstricting peptides such as angiotensin II and endothelin-1 stimulated the release of NO in the coronary artery of young rat, but the production was attenuated in the aged rat. This impaired production of NO may contribute to the greater constrictor effect of the vasoconstrictors in the aged rat. In contrast, the vasoconstrictors stimulated the release of PGI_2 to a much greater extent in aged rats than in young rats. It might be possible that aged endothelial cells could produce PGI_2 as a compensation-mechanism for reduced production of NO.To elucidate the mechanism of age-related changes in the release of NO and PGI_2, We examined the age-related changes in the expression of enzymes responsible for the synthesis of NO and PGI_2 and PGI_2 receptors to reveal the mechanism of regulation of PGI_2 production. Aorta and hearts were isolated from 3- and 27- months old Fischer 344 rats. Hearts were perfused with constant pressure (75 cmH_2O) at 37℃. Changes in the coronary flow were measured with a flow meter. 6-keto-PGF_<1α> in the coronary effluent was measured with EIA.Changes in the expression of PGI_2 receptors, NO and PGI synthase and cyclooxygenase-1 (COX-1) were quantified by real-time PCR and Western blot analysis. Release of PGI_2 into the effluent was greater in the aged rat than young rat. There was no age-related difference in the amount of PGI_2 receptor. Expression of COX-1 and PGI synthase was increased in the aged rat. These increases in COX-1 and PGI synthase may be responsible for the increased production of PGI_2 in the aged rat coronary artery. It is not yet clarified whether the expressions of NO syntase and arginine transportor change with aging.

冠状动脉疾病引起的心血管疾病的发病率随着年龄的增长而增加，内皮在调节血管张力和维持心血管功能方面发挥着重要作用。年轻大鼠的冠状动脉中存在 NO，但老年大鼠中的产生减弱。NO 的产生受损可能导致老年大鼠的血管收缩剂具有更大的收缩作用。相比之下，血管收缩剂在老年大鼠中比在年轻大鼠中刺激 PGI_2 的释放程度更大。老年内皮细胞可能会产生 PGI_2 作为 NO 产生减少的补偿机制。 NO和PGI_2释放的年龄相关变化的机制，我们检查了负责NO和PGI_2以及PGI_2受体合成的酶表达的年龄相关变化为了揭示PGI_2产生的调节机制，从3月龄和27月龄的Fischer 344大鼠中分离心脏，并在37℃下进行恒压（75 cmH_2O）灌注，并测量冠脉流量的变化。用EIA测量冠状动脉流出物中的6-酮-PGF_<1α>。PGI_2受体、NO和的表达变化。通过实时 PCR 和蛋白质印迹分析对 PGI 合酶和环氧合酶-1 (COX-1) 进行定量，老年大鼠中 PGI_2 的释放量高于年轻大鼠。 PGI_2 受体。COX-1 和 PGI 合酶的表达在老年大鼠中增加。COX-1 和 PGI 合酶的增加可能是老年大鼠中 PGI_2 产量增加的原因。冠状动脉中NO合酶和精氨酸转运蛋白的表达是否随着年龄的增长而变化尚不清楚。