Age-related changes in vascular smooth muscle and endothelium.

Aging is associated with structural and functional changes in the blood vessel wall. In vascular smooth muscle, the effects of aging on the response mediated by beta-adrenoceptors have been most intensively studied. beta-adrenoceptor-mediated relaxation decreases in most arteries, but not veins, with increasing age. In contrast, studies on contractile responses to alpha-adrenergic drugs are conflicting. The response to alpha-adrenoceptor agonists appears to be unchanged for decreased by aging. The endothelium takes part in the local regulation of vascular tone as a source of several vasoactive factors. Basal release of endothelium-derived nitric oxide decreases with age in vitro studies. Aging is also associated with reduced endothelium-dependent relaxations in response to vasoactive substances such as acetylcholine, histamine or adenosine. The impairment of the relaxation is, in most cases, achieved by a decreased release and/or decreased production of endothelium-derived relaxing factors (endothelium-derived nitric oxide, hyperpolarising factor and prostacyclin). An increased release of endothelium-derived, cyclo-oxygenase-dependent contracting factor is also responsible for reduced relaxation in some tissues. On the other hand, the release of endothelin-1 from the endothelium increases with age, while the response to the peptide decreases under the same conditions, especially in small resistance arteries. The alterations of vascular smooth muscle and endothelial cells occurring with age may have important clinical implications for the pathogenesis of cardiovascular disease.