ANATOMIC HETEROGENEITY OF VASCULAR AGING - ROLE OF NITRIC-OXIDE AND ENDOTHELIN

We investigated the effects of aging, a cardiovascular risk factor, on vascular function with regard to endothelial nitric oxide synthase (e NOS), superoxide dismutase (SOD), and endothelin (ET-1) in aorta and f emoral artery of the rat. Concentration-response curves to acetylcholi ne, calcium ionophore A23187, norepinephrine, ET-1, big endothelin, so dium nitroprusside, and exogenous SOD were obtained. Expression of eNO S mRNA was analyzed by reverse-transcription polymerase chain reaction , SOD activity was assessed using a chemiluminescence-based cytochrome c assay, and ET-1 plasma concentrations were measured by radioimmunoa ssay. In aorta of old rats, relaxations to acetylcholine and calcium-i onophore A23157, basal NO release, and expression of eNOS mRNA in aort ic endothelial cells were reduced (P<.05). In femoral arteries, relaxa tions to acetylcholine were preserved, whereas basal release of NO was attenuated (P<.05). Aging selectively increased contractions to norep inephrine and functional endothelin converting enzyme activity and att enuated contractions to ET-1 in aortas but not femoral arteries. Vascu lar SOD activity was higher in the femoral artery (P<.05) and unaffect ed by aging. Plasma ET-1 levels increased and plasma SOD activity decr eased with age (P<.05). Aging was associated with an anatomic heteroge neity of endothelial dysfunction, functional endothelin converting enz yme activity, and vascular SOD activity. Vascular function was impaire d in the aorta but not the femoral artery, which may be related to low er eNOS mRNA expression and SOD activity. These data suggest different ial regulation of the vascular aging process that may contribute to th e anatomic heterogeneity of atherosclerosis.