Autonomic Changes with Aging

Aging is associated with alterations in vascular reactivity manifesting clinically as exaggerated changes in blood pressure—hypertension and orthostatic hypotension (see Chapter 62 ). Orthostatic hypotension is quite common (about 20%) in the elderly and may result largely from diminished baroreceptor responsiveness. Heart rate response to changes in blood pressure, Valsalva maneuver, and the respiratory cycle are blunted with aging.^{[473] [474] [475] [476] [477]}

Resting and exercise-induced norepinephrine levels increase with age in healthy subjects (by about 13% per decade),^[478] in part because of decreased clearance.^{[478] [479]} Previously a matter of controversy, it now appears that besides the well-documented reduction in vagal function associated with aging,^{[480] [481]} the primary autonomic defect in aging is an impairment in norepinephrine reuptake, perhaps as a function of decreased nerve density. Although there is no apparent age-dependent decrement in nerve firing rates from sympathetic efferents in skeletal muscle,^[482] kinetic studies reveal selective and dramatic increases in cardiac norepinephrine spillover attributable to decreased reuptake in elderly patients subjected to mental stress or exercise.^[452] The augmented synaptic concentration of norepinephrine in the setting of agerelated reduction in vagal function can precipitate clinical complications (i.e., arrhythmogenesis and sudden cardiac death) in patients with cardiac disease. However, end-organ responsivenes is blunted by compensatory downregulation of the β₁ -adrenoreceptors (i.e., decreased receptor density and affinity) and uncoupling of β₂ -adrenoreceptors through decreased G_s activity.^{[483] [484] [485]} Despite increased cardiac spillover, cardiac oxygen consumption was not altered.^[486]

Attenuation of presynaptic α₂ -adrenoreceptor-mediated inhibition of neuronal norepinephrine release^{[487] [488] [489]} also accounts for increased norepinephrine levels observed with age. Reduced postsynaptic α-adrenoreceptor activity decreases contractile responses and further attenuates vasoconstrictor tone. In a seemingly vicious cycle, the increase in circulating norepinephrine levels is associated with downregulation of platelet α₂ -adrenoreceptor density and responsiveness.^[490] The loss of adrenergic control through the reduction of α₂ - and β-receptor-mediated responses with age causes a loss in the efficacy of the sympathetic system to control cardiovascular responsiveness, implying a relationship with or an explanation of the increased incidence of cardiovascular disorders such as CHF in the elderly.