Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging

Abstract

Adult aging in humans is associated with marked and sustained increases in sympathetic nervous system (SNS) activity to several peripheral tissues, including the heart, the gut-liver circulation, and skeletal muscle. This chronic activation of the peripheral SNS likely is, at least in part, a primary response of the central nervous system to stimulate thermogenesis to prevent further fat storage in the face of increasing adiposity with aging. However, as has been proposed in obesity hypertension, this tonic activation of the peripheral SNS has a number of adverse secondary cardiovascular consequences. These include chronic reductions in leg blood flow and vascular conductance, increased tonic support of arterial blood pressure, reduced limb and systemic alpha-adrenergic vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit artery hypertrophy, and decreased vascular and cardiac responsiveness to beta-adrenergic stimulation. These effects of chronic age-associated SNS activation on the structure and function of the cardiovascular system, in turn, may have important implications for the maintenance of physiological function and homeostasis, as well as the risk of developing clinical cardiovascular and metabolic diseases in middle-aged and older adults.

Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus

“…The elevation in blood pressure with age is attributable, at least in part, to an increase in sympathetic nervous activity (Esler M. et al, 2002;Esler M.D. et al, 1995;Seals and Dinenno, 2004), and sustained elevation of catecholaminergic activity requires increased levels of catecholamine biosynthesizing enzymes in the adrenal medulla and peripheral sympathetic ganglia. Our laboratory along with others have reported that TH and DβH mRNA, protein levels and enzyme activities are two-to three-fold higher in the adrenals of senescent rats compared with younger animals (Banerji et al, 1984;Kedzierski and Porter, 1990;Tumer et al, 1999;Tumer et al, 1992;Tumer and Larochelle, 1995;Voogt et al, 1990).…”

Prenatal Hypoxia Leads to Increased Muscle Sympathetic Nerve Activity, Sympathetic Hyperinnervation, Premature Blunting of Neuropeptide Y Signaling, and Hypertension in Adult Life

“…11,12 But chronically raised MSNA also occurs during aging and is accompanied by reduced reflex vasoconstriction and loss of NPY involvement in skin. 13,14 However, in young men at high altitude, chronic hypoxia caused an increase in tonic MSNA, tonic muscle vasoconstriction, and hypertension that persisted on descent to sea level. 15,16 Further, vasoconstrictor responses evoked by sympathetic activation were blunted in acute and chronic hypoxia in adult rats and humans [17][18][19] ; this was attributed to impaired vasoconstriction to NE and adenosine triphospate, but preservation of the NPY component.…”

Angiotensin II in the Elderly

“…It is well established that elevated vasoconstrictor tone as a consequence of high sympathetic nerve activity is present in healthy, older adults, [7][8][9] despite a reduction in the sensitivity of postjunctional adrenergic vascular receptors. 10 This capacity for sustained sympathetic vasoconstriction in the face of reduced adrenergic responsiveness may be suggestive of an age-related change in nonadrenergic vasoconstrictor pathways, such as Ang II.…”