Ageing and the α2-adrenergic system of the platelet

1987 ◽  
Vol 73 (5) ◽  
pp. 507-513 ◽  
Author(s):  
Pamela B. Davis ◽  
Catherine Silski

1. Platelets taken from healthy unmedicated subjects over 65 years of age display less inhibition of prostaglandin E1 (PGE1)-stimulated adenosine 3′:5′-cyclic monophosphate (cyclic AMP) synthesis by noradrenaline than do platelets taken from young adults aged 18–25 years (P < 0.03). The inhibition of cyclic AMP production by noradrenaline (10−5 mol/l) correlates negatively with age over the range 18–92 years (r = −0.338, n = 108, P < 0.005). The reduced cyclic AMP inhibition by noradrenaline in the elderly is not explained by basal cyclic AMP levels or degree of stimulation of platelets by PGE1, which do not differ between young and elderly subjects. The reduction itself is small, though, and cannot be demonstrated for a more potent agonist, adrenaline. 2. Despite the reduced noradrenaline response in the cyclic AMP system in the aged, platelet aggregation in response to α2-adrenergic agents is normal or even slightly increased. Aggregation responses to adrenergic agents correlate well with aggregation responses to adenosine 5′-diphosphate, suggesting that the effector system is a major determinant of the aggregation response. 3. α2-Adrenoceptor number measured by Scatchard analysis of equilibrium binding of [3H]yohimbine to platelet membranes is comparable in young and old subjects, and does not correlate with age. The KD for [3H]yohimbine does not correlate with age. The IC50 for noradrenaline displacing [3H]yohimbine is comparable in young and elderly subjects. Therefore the reduced inhibition of cyclic AMP production by noradrenaline in platelets from elderly subjects is not explained by changes in α2-adrenoceptor number, or agonist- or antagonist-binding properties, but may reside in the coupling of receptor to cyclase.

1983 ◽  
Vol 65 (2) ◽  
pp. 155-157 ◽  
Author(s):  
T. G. Cotter ◽  
K. O'Malley

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05). 2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found. 3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population. 4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.


1994 ◽  
Vol 37 (3) ◽  
pp. 662-670 ◽  
Author(s):  
Peter J. Fitzgibbons ◽  
Sandra Gordon-Salant

This study examined auditory temporal sensitivity in young adult and elderly listeners using psychophysical tasks that measured duration discrimination. Listeners in the experiments were divided into groups of young and elderly subjects with normal hearing sensitivity and with mild-to-moderate sloping sensorineural hearing loss. Temporal thresholds in all tasks were measured with an adaptive forced-choice procedure using tonal stimuli centered at 500 Hz and 4000 Hz. Difference limens for duration were measured for tone bursts (250 msec reference duration) and for silent intervals between tone bursts (250 msec and 6.4 msec reference durations). Results showed that the elderly listeners exhibited diminished duration discrimination for both tones and silent intervals when the reference duration was 250 msec. Hearing loss did not affect these results. Discrimination of the brief temporal gap (6.4 msec) was influenced by age and hearing loss, but these effects were not consistent across all listeners. Effects of stimulus frequency were not evident for most of the duration discrimination conditions.


1991 ◽  
Vol 261 (2) ◽  
pp. E252-E256 ◽  
Author(s):  
B. A. Clark ◽  
D. Elahi ◽  
L. Fish ◽  
M. McAloon-Dyke ◽  
K. Davis ◽  
...  

Atrial natriuretic peptide (ANP) may suppress vasopressin release, but the dynamics of this interaction as well as the influence of age have not been defined. We studied six or seven young (19-40 yr old) and seven elderly volunteers (65-83 yr old) under two circumstances: 1) after infusion of 5% saline (0.04 ml.kg-1.min-1) for 2 h and 2) after the same infusion given with simultaneous synthetic human ANP (0.05 micrograms.kg-1.min-1). Hypertonic saline alone produced a progressive rise in plasma vasopressin with increasing serum sodium. During hypertonic saline alone, vasopressin levels began to rise at an increment in serum sodium of 1.67 +/- 0.35 mM in the young and 1.43 +/- 0.32 mM in the elderly and rose linearly with increasing serum sodium. When ANP was infused with hypertonic saline (with peak ANP levels of approximately 1,000 pM), vasopressin levels began to rise at an increment in serum sodium of 4.43 +/- 0.67 mM in the young and 4.57 +/- 0.43 mM in the elderly (P less than 0.01 vs. saline alone). Furthermore, the vasopressin response for any given serum sodium was significantly reduced in both young and elderly subjects, resulting in a rightward displacement of the curve relating vasopressin response to sodium concentration (P less than 0.001). In conclusion, ANP not only suppresses vasopressin but raises the threshold for release of vasopressin in response to osmotic stimulation in both young and elderly individuals. High circulating ANP levels may be responsible in part for the suppression of vasopressin levels and water diuresis seen during states of volume expansion.


1994 ◽  
Vol 77 (6) ◽  
pp. 2648-2658 ◽  
Author(s):  
D. A. Keen ◽  
G. H. Yue ◽  
R. M. Enoka

The increase in motor unit force that occurs with aging has been hypothesized to cause a decline in the ability to maintain a constant submaximal force. To test this hypothesis, young and elderly subjects performed a 12-wk strength-training program that was intended to increase motor unit force. The training program caused similar increases (%initial) in the training load (137.4 +/- 17.2%), twitch force (23.1 +/- 7.4%), and maximum voluntary contraction force (39.2 +/- 6.8%) of the first dorsal interosseus muscle for the young and elderly subjects. The increase in strength was associated with a modest increase in muscle volume (7% of initial value) and a nonmonotonic increase in the surface-recorded electromyogram that was significant at week 8 but not at week 12. The elderly subjects reduced the variability in force at the lower target forces (2.5, 5.0, and 20.0% maximum voluntary contraction force). This improvement, however, was unrelated to changes in the distribution of motor unit forces, which was not consistent with the hypothesis that the greater coefficient of variation for the force fluctuations is due to increased motor unit forces.


1997 ◽  
Vol 77 (5) ◽  
pp. 721-729 ◽  
Author(s):  
Daphne L. E. Pannemans ◽  
Gertjan Schaafsma ◽  
Klaas R. Westerterp

The present study was conducted to investigate the effect of dietary protein on urinary Ca excretion, apparent Ca absorption and Ca balance in young and elderly subjects. Young adults (n 29) and elderly persons (n 26) consumed diets containing 12% (diet A) and 21% (diet B) of total energy as protein for 3 weeks according to a randomized crossover design. Results showed no differences between the two age groups with respect to the interaction between protein intake and Ca excretion (both in urine and in faeces), apparent Ca absorption and Ca balance. Therefore analyses were done for both age groups separately and also for the whole group. In elderly persons and in the whole group the Ca excretion in faeces (as a percentage of Ca intake) was lower during the higher protein intake (elderly: diet A, 106 (SEM 7)% diet B, 86 (SEM 7) % P = 0·018; whole group: diet A, 99 (SEM 4) % diet B, 84 (SEM 4) % P = 0·003). In young adults faecal Ca excretion tended to be lower when they consumed diet B (diet A: 94 (SEM 5)% diet B: 83 (SEM 6)% P = 0·093). Relative urinary Ca excretion was greater during the higher protein intake in young adults and in the whole group while relative urinary Ca excretion was not different in the elderly (diet A: 15 (SEM 1) %, 14 (SEM 1) %, 15 (SEM 1) % diet B: 16 (SEM 1) %, 16 (SEM 1) % 17 (SEM 2) % for the whole group, the young and elderly subjects respectively, P = 0·019; P = 0·016; P = 0·243).The resulting Ca balance was not influenced by the amount of protein in the diet in young adults. Values for the elderly and for the whole group showed that the Ca balance during diet A was significantly more negative compared with Ca balance during diet B, despite the higher urinary Ca excretion during diet B. It can be concluded that increasing the protein intake from 12 to 21% of total energy ntake had no negative effect on Ca balance.


1997 ◽  
Vol 272 (2) ◽  
pp. G233-G237 ◽  
Author(s):  
P. Xie ◽  
J. Ren ◽  
E. Bardan ◽  
R. K. Mittal ◽  
Z. Sui ◽  
...  

Earlier studies have shown that isolated complete lower esophageal sphincter (LES) relaxation occurs as a result of pharyngeal water stimulation. Association of these relaxations with gastroesophageal reflux has not been studied systematically. Our aim was to determine this association in young and elderly subjects during precibal and postprandial periods. We studied 8 young subjects and 10 elderly subjects for 1 h before and 2 h after a 1,000-cal meal. In both groups, during the precibal period, negligible LES relaxation induced by pharyngeal water stimulation resulted in gastroesophageal reflux. In the postprandial period, gastroesophageal reflux events occurred after 16% of pharyngeal water injections in young subjects and after 44% in elderly subjects (P < 0.05). Intraabdominal length of the LES in elderly subjects was significantly shorter compared with younger subjects (P < 0.05). We conclude that gastroesophageal reflux events induced by pharyngeal water stimulation in the postprandial period are significantly increased compared with those of the precibal period and are significantly more prevalent in the elderly compared with the young. These differences seem to be associated with a significantly shorter intra-abdominal segment of the LES in the elderly.


VASA ◽  
2015 ◽  
Vol 44 (1) ◽  
pp. 43-48
Author(s):  
Kunihiko Tanaka ◽  
Kimiko Kamihira ◽  
Fumie Minoura ◽  
Miyuki Watanabe ◽  
Emi Fujiyoshi ◽  
...  

Background: The second derivative of the finger plethysmogram (SDPTG) comprises five waves termed a to e. The magnitudes of waves b-e are normalized by that of wave a for within- and between-patient comparison. In the present study, affects of meal ingestion for SDPTG in young and elderly subjects are examined. Subjects and methods: Mean arterial pressure and SDPTG before and after meal ingestion in young and elderly subjects were measured. For young subjects, stroke volume and pulse rate were also measured, and the total peripheral resistance (TPR) of the blood vessels was analyzed. Relationship between TPR and the ratio of the peak of SDPTG in young subjects was also analyzed. Results: In young subjects, postprandial d/a was significantly larger and TPR was smaller than before intake and was linearly and significantly correlated with TPR. An increase in the postprandial d/a was also observed in the elderly subjects who were not undergoing hypertension treatment. However, this increase was not observed in elderly subjects who were treated for hypertension. Conclusions: Change in d/a is considered to be an index of change in TPR. TPR is considered to be decreased by agents for treatment of hypertension, and meal ingestion does not appear to further decrease TPR. These results are considered to be useful for understanding cardiodynamics surrounding meal ingestion.


AGE ◽  
1984 ◽  
Vol 7 (3) ◽  
pp. 71-74 ◽  
Author(s):  
J. Stessman ◽  
R. Eliakim ◽  
R. P. Ebstein

1981 ◽  
Author(s):  
David C Stump ◽  
Donald E Macfarlane

Epinephrine induces platelet aggregation, potentiates aggregation by other agents, and blocks the stimulation of the adenylate cyclase by prostaglandins. Synthetic α-adrenergic agents have not been shown to induce aggregation. The effects of clonidine, an α2-agonist, and ρ-aminoclonidine on platelets were examined. Clonidine potentiated aggregation induced by 0.5μM ADP by 1.4-fold (1/2 max 0.5μM). It did not induce significant aggregation itself, and it inhibited aggregation induced by 5μM epinephrine (1/2 max lμM). It inhibited cyclic AMP accumulation induced by PGE1 by a maximum of 25% (1/2 max O.lμM) and it blocked inhibition by epinephrine. No significant specific binding of [3H] clonidine was observed to intact platelets. ρ-Aminoclonidine induced aggregation with delayed second phase (1/2 max 0.2μM), and potentiated ADP aggregation by 2-fold (1/2 max 0.2μM). Aggregation induced by epinephrine was more rapid, and was partially inhibited by ρ-aminoclonidine. It inhibited cyclic AMP accumulation by 50% max (1/2 max O.lμM) and attenuated epinephrine’s effect to the same level. The direct effects of ρ-aminoclonidine were blocked by lμM yohimbine, a selective α2-antagonist. Both clonidine and ρ—aminoclonidine blocked the specific binding of [3H]yohimbine (1/2 max 0.5μM). These results suggest that the platelet bears an α2-receptor with affinity for epinephrine, ρ-aminoclonidine and clonidine as agonists but that these agents display differing intrinsic activity and/or receptor reserve.


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