Possible Mechanisms of Age-associated Decrease in Vascular Functions

年龄相关的血管功能下降的可能机制

• 批准号: 63571045
• 负责人: MORITOKI Hideki
• 金额: $ 1.34万
• 依托单位: Faculty of Pharmaceutical Sciences, 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: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571045/
• 关键词: Aging; Vascular function; Vascular endothelium; Vasodilation; Cyclic GMP; Antiaggregating activity; Phosphodiesterase; Vitamin E; サイクリック ヌクレオチド; ホスフォジエステラ-ゼ; 過酸化脂質; 血管内皮細胞; 血管灌流; 抗血小板凝集活性; 血管拡張アセチルコリン; ATP; プロスタサイクリン

The effect of aging on vascular functions were examined.Aging reduced the endothelium-dependent dilator responses of rat thoracic aorta to vasodilators, such as acetylcholine, histamine, ATP and adenosine. Loss of the dilator responses was found to be associated with reduction of cGMP formation. These changes may be due to both reduction in ability of the endothelium to produce endothelium-derived relaxing factor (EDRF) and/or prostacyclin, and also decrease in guanylate cyclase activity.The inhibitory effects of the cGMP-phosphodiesterase inhibitors M&B 22948 and dipyridamole on the phenylephrine-induced contraction, and accumulation of cGMP in the presence of M&B 22948 were greater in the arteries from old rats than those from young rats. These results suggest that with increase in age, hydrolysis of cGMP by cGMP-phosphodiesterase is accelerated, thus decreasing cGMP-dependent dilator response.In the case of adenosine, specific binding sites of [^3H]NECA, a A2-adenosine receptor liga … More nd, decreased during aging. Reduction of the number of adenosine receptors in vascular smooth muscle could be responsible for the age-associated reduction of the dilator response and cGMP formation.In addition to these changes, the activity of the endothelium to prevent platelet aggregation was also shown to be lower in the arteries from old rats. When the lumen of the arteries was perfused with Krebs solution containing acetylcholine, histamine or ATP, the luminal perfusate of the arteries from young rats effectively inhibited ADP-induced aggregation. The results suggest that the endothelium produces some anti-aggregating substance, probably prostacyclin, and that production of this substance decreases during aging.A preliminary study on the effect of vitamin E deficiency and supplement on the responses of rat arteris to vasodilators was carried out. VE deficiency accelerated the age-associated decrease in dilator responses, whereas VE supplement protected the arteries from this change. Less

衰老降低大鼠胸主动脉对血管舒张剂如乙酰胆碱、组胺、ATP和腺苷的内皮依赖性舒张反应。发现扩张器反应的丧失与cGMP形成的减少有关。cGMP磷酸二酯酶抑制剂M&B 22948和潘生丁对苯肾上腺素引起的收缩的抑制作用，在M&B 22948存在下，老年大鼠动脉中cGMP的浓度和累积量大于年轻大鼠。这些结果表明，随着年龄的增长，cGMP磷酸二酯酶对cGMP的水解加速，从而降低cGMP依赖性扩张反应。 ...更多信息 nd，在老化过程中下降。血管平滑肌中腺苷受体数量的减少可能是与年龄相关的扩张反应和cGMP形成减少的原因。除了这些变化外，老年大鼠动脉中内皮细胞阻止血小板聚集的活性也较低。用含乙酰胆碱、组胺或ATP的Krebs液灌流动脉管腔，幼鼠动脉管腔灌流液能有效地抑制ADP诱导的聚集。结果提示，血管内皮细胞产生抗聚集物质，可能是前列环素，随着年龄的增长，这种物质的产生减少。本文初步研究了维生素E缺乏和补充对大鼠动脉对血管扩张剂反应的影响。维生素E缺乏加速了与年龄相关的扩张反应的下降，而维生素E补充剂保护动脉免受这种变化。少

项目成果

Moritoki,H.,et al.: British J.Pharmacology. 95. 1015-1022 (1988)

Moritoki,H.,et al.：British J.Pharmacology。

Moritoki,H.et al.: "Possible mechsanisms of age-associated changes in vascular function in:Biosignaling in Cardiac and Vascular Systems," Pergamon Press,

Moritoki,H.et al.：“心脏和血管系统中的生物信号传导与年龄相关的血管功能变化的可能机制”，佩加蒙出版社，

Moritoki,H.,Tanioka,A.Ueda,H.: "Does cGMP mediate adenosine-induced vasodilation? in:Biosignaling in Cardiac and Vascular systems." Eds.Fujiwara et al.,Pergamon Press,Oxford, 292-295 (1989)

Moritoki,H.,Tanioka,A.Ueda,H.：“cGMP 是否介导腺苷诱导的血管舒张？见：心脏和血管系统的生物信号传导。”

Moritoki,H.,Matsugi,T.,Takase,H.,Ueda,H.&Tanioka,A.: "Evidence for the involvement of cyclic GMP in adenosineーinduced ageーdependent vasodilataion." Brit.J.Pharmacol..,.

Moritoki, H.、Matsugi, T.、Takase, H.、Ueda, H. 和 Tanioka, A.：“环 GMP 参与腺苷诱导的年龄依赖性血管舒张的证据。” , .

Moritoki,H,.Tanioka,A.,Matsugi,T.&Takase,H.: "Indication of possible association of decrease in cGMP-mediated vaso-dilation with increase in c GMP-phosphodiesterase activity during aging.:in Biosignaling in Cardiac and Vascular Systems." Eds.Fujiwara et a

森时，H，.谷冈，A.，松木，T.