AGE-RELATED-CHANGES IN VASCULAR SMOOTH-MUSCLE AND ENDOTHELIUM

Aging is associated with structural and functional changes in the bloo d vessel wall. In vascular smooth muscle, the effects of aging on the response mediated by beta-adrenoceptors have been most intensively stu died. beta-Adrenoceptor-mediated relaxation decreases in most arteries , but not veins, with increasing age. In contrast, studies on contract ile responses to alpha-adrenergic drugs are conflicting. The response to alpha-adrenoceptor agonists appears to be unchanged or decreased by aging. The endothelium takes part in the local regulation of vascular tone as a source of several vasoactive factors. Basal release of endo thelium-derived nitric oxide decreases with age in in vitro studies. A ging 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, ach ieved by a decreased release and/or decreased production of endotheliu m-derived relaxing factors (endothelium-derived nitric oxide, hyperpol arising factor and prostacyclin). An increased release of endothelium- derived, cyclo-oxygenase-dependent contracting factor is also responsi ble for the reduced relaxation in some tissues. On the other hand, the release of endothelin-l from the endothelium increases with age, whil e the response to the peptide decreases under the same conditions, esp ecially in small resistance arteries. The alterations of vascular smoo th muscle and endothelial cells occurring with age may have important clinical implications for the pathogenesis of cardiovascular disease.