Age-associated changes in beta-adrenergic modulation on rat cardiac excitation-contraction coupling.

Abstract

Previous studies have demonstrated that the ability of (.-adrenergic receptor (.BAR) stimulation to increase cardiac contractility declines with aging. In the present study, the control mechanisms of excitation-contraction (EC) to NE were proportional to the reductions in the Ic response. These findings suggest that the observed age-associated reduction in fAR modulation of the cardiac contraction is, in part at least, due to a deficit in modulation of Ca?+, particularly the activity of L-type calcium channels.(J. Clin. Invest. 1994. 94:2051-2059

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

“…A reduced myocardial contractile response to either ␤ 1 AR or ␤ 2 AR stimulation is observed with aging. 74 -76 This is due to failure of ␤AR stimulation to augment Ca i to the same extent in cells of senescent hearts that it does in those from younger adult hearts, 74 an effect attributable to a deficient increase of L-type sarcolemmal Ca 2ϩ channel availability, which leads to a lesser increase in Ca 2ϩ influx. 74 The richly documented age-associated reduction in the postsynaptic response of myocardial cells to ␤AR stimulation seems to be due to multiple changes in the molecular and biochemical steps that couple the receptor to postreceptor effectors.…”

“…74 -76 This is due to failure of ␤AR stimulation to augment Ca i to the same extent in cells of senescent hearts that it does in those from younger adult hearts, 74 an effect attributable to a deficient increase of L-type sarcolemmal Ca 2ϩ channel availability, which leads to a lesser increase in Ca 2ϩ influx. 74 The richly documented age-associated reduction in the postsynaptic response of myocardial cells to ␤AR stimulation seems to be due to multiple changes in the molecular and biochemical steps that couple the receptor to postreceptor effectors. However, the major limiting modification of this signaling pathway that occurs with advancing age in rodents seems to be the coupling of the ␤-adrenergic receptor to adenylyl cyclase via the Gs protein and changes in adenylyl cyclase protein, which lead to a reduction in the ability to sufficiently augment cell cAMP and to activate protein kinase A to drive the phosphorylation of key proteins that are required to augment cardiac contractility.…”

Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations

“…These age-dependent changes lead to a prominent decline in cardiac function, which may cause elderly people to be more prone to various cardiovascular diseases. The cardiac contractionrelaxation cycle has been shown to alter with age, most likely due to dysregulation of cytosolic calcium homeostasis [1,2]. In cardiomyocytes, a typical contraction-relaxation cycle is initiated by opening of L-type Ca 2+ channel (LTCC) which triggers the opening of the ryanodine receptor (RYR) and gives rise to a global intracellular Ca 2+ increase.…”

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

“…Age-related changes in human and rodent hearts include a reduction in the number of myocytes (10,11), myocyte hypertrophy (11,12), cardiac fibrosis (13), lipofuscin pigment accumulation (14), a reduction in calcium transport across sarcoplasmic reticulum membrane (15), and alterations in the response to ␤-adrenergic stimulation (16). Collectively, these alterations likely contribute to age-related heart diseases being the leading cause of mortality in the U.S. (17).…”