β-adrenergic receptor responsiveness in aging heart and clinical implications

Abstract

Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called “β-adrenergic desensitization”). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure.

Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans

“…Interestingly, compared with the large effect in young individuals, fentanyl blockade had a substantially smaller, but still significant, effect on cardiac output in the old (ϳ5% decrease), a discrepancy suggestive of an age-related decline in the role of the group III/IVmediated muscle reflexes in facilitating central hemodynamics during exercise. The small effect of the afferent blockade on cardiac output in the old is likely attributable to the age-related impairment in the autonomic regulation of the heart, a phenomenon which is largely accounted for by ␤-adrenergic desensitization (14).…”

“…Specifically, changes in myocardial contractile properties, impairments in the autonomic regulation of the heart via ␤-adrenergic desensitization, vascular dysfunction, and changes in the baroreflex control of blood pressure have all been documented to occur with advancing age (14,15,28,37). Although many of these changes are a direct consequence of aging, others may actually be appropriate secondary adaptations that ensure the correct autonomicly mediated cardiovascular response to these original physiological changes in older individuals.…”

Cardiac aging and heart disease in humans

“…With aging, circulating catecholamine levels increase, leading to a reduction of β-adrenergic receptor density at the plasma membrane. This explains the reduced β-adrenergic responsivity observed with age, defined as β-adrenergic desensitization (Ferrara et al 2014). In addition, chronic β-adrenergic stimulation may induce ROS production leading to heart damage (Dai et al 2012).…”

Beta-blockers and aerobic training on peripheral adrenoceptor numbers in CAD patients

“…Indeed, mounting evidence indicates that adrenergic receptors are functionally involved in numerous processes underlying cardiovascular disorders [4].…”