Abstract

The effect of age on cholinergic endothelium-mediated relaxation was examined in vitro using blood vessels from Fischer 344 rats ranging in age from 1 to 27 months. Although no differences were seen in contractile response to alpha adrenergic agonists, both aortic ring segments and perfused caudal arteries showed an increase in sensitivity of endothelium-mediated relaxation to the cholinergic agonist methacholine. This increase in sensitivity occurs between the ages of 6 and 12 months, with no further significant increase in sensitivity up to 27 months of age, suggesting it is a consequence of growth and development rather than old age. No difference with age in cholinergic relaxation was observed in the perfused mesenteric bed, indicating either no change of sensitivity in smaller resistance vessels or an effect that is hidden in this more complex perfused system. In contrast to findings with cholinergic stimulation, responses of the perfused caudal artery to the calcium ionophore A23187 were not altered with age. This suggests that the alteration with age in response to methacholine involves the muscarinic receptor or receptor-coupling mechanism rather than the generation of, or response to, endothelium-derived relaxing factor.