Possible Mechanisms of Age-associated Decrease in Vascular Functions

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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