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

1. 研究了衰老对大鼠胸主动脉血管扩张剂引起的血管扩张、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随着大鼠年龄的增加而逐渐降低，在60周龄以上的大鼠的制剂中，不再检测到扩张剂反应。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积累，cAMP水平无变化。cGMP水平的增加也随着年龄的增长而下降。内皮的去除完全消除了血管的扩张和cGMP的积累。这些结果表明，衰老降低了内皮细胞产生内皮源性松弛因子（EDRF）的能力，内皮源性松弛因子可以刺激环化酶。从而减少cGMP的积累。因此，随着年龄的增长，主动脉对血管扩张剂的反应减弱，可能是由于内皮功能的逐渐丧失和谷烷酸环化酶活性的减少。接下来，我们研究了内皮细胞阻止血小板聚集的能力是否也随着年龄的增长而下降。血管腔内灌注含乙酰胆碱的克雷布斯溶液。7 .先用灌注液孵育富血浆血小板，然后加入ADP诱导血小板聚集。幼龄大鼠动脉灌注液能有效抑制adp诱导的聚集。随着大鼠年龄的增加至100周龄，灌注液的抗聚集活性明显降低。内皮剥蚀导致抗聚集活性完全丧失。这表明一种阻止聚集的物质来源于内皮细胞。环加氧酶抑制剂吲哚美辛也能抑制抗聚集活性，表明pgs的介导作用。因此，这些结果表明，内皮细胞对血管舒张剂产生一定的抗聚集物质，可能是PGI_2，这种物质的产生随着年龄的增长而减少。少

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