Possible Mechanisms of Age-associated Decrease in Vascular Functions

研究了衰老对血管功能的影响。衰老降低了大鼠胸主动脉对乙酰胆碱、组胺、三磷酸腺苷和腺苷等血管扩张剂的内皮依赖性扩张剂的反应。扩张器反应的丧失被发现与cGMP形成的减少有关。这些变化可能是由于内皮细胞产生内皮衍生松弛因子和/或前列环素的能力降低以及鸟苷环化酶活性的降低所致。环鸟苷酸磷酸二酯酶抑制剂M&B 22948和双嘧达莫对苯肾上腺素诱导的收缩和在M&B 22948存在下的环鸟苷酸蓄积的抑制作用在老年大鼠比青年大鼠更大。这些结果表明，随着年龄的增加，cGMP-磷酸二酯酶对cGMP的水解率加快，从而降低了cGMP依赖的扩张器反应。在腺苷的情况下，A2-腺苷受体LIGA…的特异性结合部位随着年龄的增长，更多的ND减少。血管平滑肌上腺苷受体数量的减少可能是与年龄相关的扩张器反应和cGMP形成减少的原因。除了这些变化外，老年大鼠动脉中防止血小板聚集的内皮活性也被证明是较低的。当动脉腔内灌流含有乙酰胆碱、组胺或三磷酸腺苷的Krebs液时，幼年大鼠动脉腔灌流液可有效地抑制ADP诱导的聚集。结果提示，血管内皮细胞产生一些抗聚集物质，可能是前列环素，这种物质的产生随着年龄的增长而减少。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器反应的下降，而补充维生素E则保护动脉免受这种变化的影响。较少

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