Age-related changes in vascular adrenergic signaling: clinical and mechanistic implications

A large and growing segment of the general population are age 65 or older, and this percentage will continue to rise. Primary care of this population has, and is becoming a priority for clinicians. Hypertension, orthostatic hypotension, arterial insufficiency, and atherosclerosis are common disorders in the elderly that lead to significant morbidity and mortality. One common factor to these conditions is an age-related decline in beta-adrenergic receptor (beta-AR)-mediated function and subsequent cAMP generation. Presently, there is no single cellular factor that can explain this age-related decline, and thus the primary cause of this homeostatic imbalance is yet to be identified. However, the etiology is clearly associated with an age-related change in the ability of beta-AR receptor to respond to agonist at the cellular level. This article will review what is presently understood regarding the molecular and biochemical basis of age-impaired beta-AR receptor-mediated signaling. A fundamental understanding of why beta-AR-mediated vasorelaxation is impaired with age will provide new insights and innovative strategies for the management of the multiple clinical disorders that effect older people. (C) 2002 Published by Elsevier Science Ireland Ltd.