Age‐related changes in adenosine and beta‐adrenoceptor responsiveness of vascular smooth muscle in man.

Abstract

1 Ageing is associated with a decline in ,3-adrenergic responsiveness in several tissues.Reduced ,-adrenoceptor mediated smooth muscle relaxation in aged man has been demonstrated using the dorsal hand vein technique. Isoprenaline and adenosine activate adenylate cyclase through separate membrane bound receptors to induce vasodilatation.2 To determine the specificity of reduced ,-adrenergic responsivenes.s in smooth muscle of aged man, and possible sites of the defect responsible, venodilatory responses to isoprenaline, a ,B-adrenoceptor agonist and adenosine were determined in nine young (age 26 ± 3 years: mean ± s.d.) and eight elderly (age 70 ± 5 years), healthy male volunteers. Veins were partially constricted with the axl-adrenoceptor agonist phenylephrine and increasing doses of adenosine (5 to 1220 ,ug min-') or isoprenaline (271 ng min-1) were infused. 3 Maximal dilatation induced by isoprenaline was 83 ± 26% in the young and 51 ± 34% in the elderly, P = 0.02. Maximal dilatation induced at th-highest dose of adenosine (1220 jig min-') was similar in young and elderly: 79 ± 25% vs 88 ± 28%, P = 0.26.4 Adenosine venodilatation was measured before and after infusions of theophylline (6.8 to 135 ,ug min-') for 30 min in six subjects. Adenosine responsiveness was unchanged following theophylline: 48 ± 16% to 49 ± 40%, P = 0.44. 5 The results suggest that the age-associated reduced responsiveness of the ,3-adrenergic system in human vascular smooth muscle is not shared by venodilatation mediated by adenosine.

Baseline heart rate variability in healthy centenarians: differences compared with aged subjects (>75 years old)

“…Under supine conditions and during normal breathing conditions, the relative balance between LF and HF components does not differ between young and older subjects [23]. On the other hand, the finding that agerelated differences in HRV in the supine state were largely eliminated by the administration of atropine and propranolol suggests that age-related differences in HRV, in contrast with those in heart rate, can be explained solely on the basis of parasympathetic and β-adrenergic influences [18,19]. Thus one can conclude that differences between aged subjects and healthy centenarians might be due to a negative impact of advancing age on ANS activity.…”

“…Several hypotheses can be suggested for explaining our results. In vitro and in vivo data show that resting heart rate appears to be only slightly changed by aging in healthy adult humans, while the heart rate response to exercise, to β-adrenergic stimulation and blockade and to parasympathetic blockade with atropine diminishes with aging [18,19]. Beat-to-beat variability of heart rate also decreases with increasing age [20,21].…”

Genetic Variation in the β2-Adrenergic Receptor: Impact on Intermediate Cardiovascular Phenotypes

“…This means that if β 2 -receptor mediated dilation is blunted, the pressor response to mental stress is likely to be increased. Consistent with these general ideas are a number of observations primarily from the pre-genomic era: 1) The pressor response to mental stress is heritable [Busjahn, A. et al 2000; Carmelli, D. et al 1985; Carmelli, D. et al 1991; Li, G. H. et al 2001; McCaffery, J. M. et al 2002]; 2) β 2 -mediated forearm vasodilator responses to mental stress are blunted in subjects thought to be at increased risk for hypertension and in individuals with mild hypertension [Cardillo, C. et al 1998; Cardillo, C. et al 1998; Hughes, J. W. et al 2003]; 3) Vasodilator responses to brachial artery, or systemic infusions of β-agonists are blunted in subjects thought to be at increased risk for hypertension, and in mild hypertension [Dimsdale, J. et al 1988; Feldman, R. D. 1987; Feldman, R. D. 1990; Ford, G. A. et al 1992; Halliwill, J. R. et al 1997; Lang, C. C. et al 1995; Sherwood, A. and Hinderliter, A. L. 1993; Stein, C. M. et al 1995; Watkins, L. L. et al 1995]. …”

Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes

“…Experimental findings indicate an age-associated decrease in catecholamine-responsiveness in the elderly, documenting a decreased βAR vasorelaxation with ageing [33-35]. Indeed, younger individuals are more responsive than elderly subjects to isoproterenol-induced increases in blood flow in the brachial artery [36].…”