Age-related decrease in vqsodilation and anti-aggregating function of vascular endothelium

血管内皮血管舒张和抗聚集功能与年龄相关的下降

• 批准号: 60571048
• 负责人: MORITOKI Hideki
• 金额: $ 0.45万
• 依托单位: University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60571048/
• 关键词: Aging; Vasodilation; Endothelium; cGMP; サイクリックGMP; 内腔潅流液; 抗血小板活性; 血管拡張反応減弱; 血管内膜; 血小板凝集阻止能; 血管拡張剤; フリーラジカル; アデノシン; ヒスタミン

1. Effects of aging on the dilation caused by vasodilators and the formation of cGMO, and anti-aggregation activity of endothelium of vessels were studied on rat thoracic aorta.2. Endothelium-dependent vasodilation progressively decreased with increase in age of rats, and in preparations from rats of over 60 weeks old, the dilator response was no longer detectable.3. Histamine, acetylcholine, adenosine or nitrovasodilators induced cGMP accumulation in aorta from rats of 8 weeks old, with no change in cAMP level. This increase in cGMP level also decreased with aging.4. Removal of the endothelium completely abolished the dilation and the cGMP accumulation.5. These results suggest that aging reduces the ability of the endothelium to produce endothelium derived relaxing factor (EDRF), which stimulates quanylate cyclase. and so decreawes cGMP accumulation.6. Thus the decreased dilator response of the aorta to vasodilators during aging is probably due to both gradual loss of endothelium func … More tion and reduction of guqnylate cyclase activity.7. Next, we examined whether the ability of endothelium to prevent platelet aggregation also decreased with aging. Lumen of the vessels was perfused with Krebs solution containing acetylcholine. Plasma rich platelet was first incubated wiht the perfusate, and then ADP was added to induce aggregation.8. The perfusate of the artery from young rats effectively inhibited ADP-induced aggregation.9. With increase in age of rats to 100 weeks, the anti-aggregating activity of the perfusate significantly decreased.10. Endothelium denudation caused complete loss of the anti-aggregating activity. This indicates that a substance which prevents aggregation, originates from the endothelium.11. The cyclooxygenase inhibitor indomethacin also abolished anti-aggregating activity, indicating mediation of PGs.12. Thus, these results suggest that endothelium produces some anti-aggregating substance, probably PGI_2, in response to vasodilators and this production is reduced by aging. Less

1.在大鼠胸主动脉模型上研究增龄对血管舒张剂引起的血管舒张作用、cGMO形成及血管内皮抗聚集活性的影响.内皮依赖性血管舒张功能随着大鼠年龄的增加而逐渐降低，在60周龄以上的大鼠中，不再检测到扩张反应.组胺、乙酰胆碱、腺苷或硝基血管扩张剂诱导8周龄大鼠主动脉cGMP积聚，cAMP水平无变化。cGMP水平的增加也随着年龄的增长而下降。去除内皮后，血管舒张功能完全消失，cGMP的积聚也消失.这些结果表明，老化降低了内皮细胞产生内皮源性舒张因子（EDRF）的能力，EDRF可刺激量子环化酶。从而减少cGMP的积累。因此，衰老过程中主动脉对血管扩张剂的扩张反应降低可能是由于内皮功能逐渐丧失， ...更多信息 抑制和降低胍基酸环化酶活性。接下来，我们研究了内皮细胞防止血小板聚集的能力是否也随着年龄的增长而下降。用含乙酰胆碱的Krebs溶液灌注血管腔。首先将富含血浆的血小板与灌流液一起孵育，然后加入ADP以诱导聚集。幼鼠动脉灌流液能有效抑制ADP诱导的血管聚集.随着大鼠年龄的增加至100周龄，灌流液的抗聚集活性显著降低。内皮剥脱导致抗聚集活性完全丧失。这表明一种防止聚集的物质源自内皮。11.环氧合酶抑制剂吲哚美辛也消除了抗聚集活性，表明PG的介导。这些结果提示内皮细胞对血管扩张剂有反应，产生抗聚集物质，可能是PGI_2，而这种产生随着年龄的增长而减少。少

项目成果

Moritoki,H., Hosoki,E. & Ishida,Y.: "Age-related decrease in endothelium-dependent dilator response to histamine inrat mesenteric artery" European J. Pharmacology. 126. 61-67 (1986)

森时，H.，细木，E.

Moritoki,H.;Hosoki,E.& Ishida,Y.: European J.Pharmacology. 126. 61-67 (1986)

森时，H.；细木，E.

Moritoki,H., Iwamoto,T., Kanaya,J., Ishida,Y. & Fukuda,H.: "Age-related change in serotonin-mediated prejunctional inhibition of rat vas deferens" European J. Pharmacology. 132. 39-46 (1987)

森时，H.，岩本，T.，金谷，J.，石田，Y。

Moritoki,H.;Iwamoto,T.;Kanaya,J.;Ishaida,Y.;Fukuda,H.: European J.Pharmacology. 132. 39-46 (1986)

Moritoki，H.；Iwamoto，T.；Kanaya，J.；Ishaida，Y.；Fukuda，H.：欧洲药理学杂志。

守時英喜,岩本武史,石田行雄: 日本平滑筋誌. 23. 390-392 (1987)

Hideki Moritoki、Takeshi Iwamoto、Yukio Ishida：日本平滑肌杂志 23. 390-392 (1987)。