| Co-Investigator(Kenkyū-buntansha) |
HORIO Shuhei Faculty of Pharmaceutical Sciences, University of Tokushima,, 薬学部, 助手 (80145010)
FUKUZAWA Kenji Faculty of Pharmaceutical Sciences, University of Tokushima,, 薬学部, 助教授 (90035551)
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| Research Abstract |
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
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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
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