The effect of ageing on human platelet sensitivity to serotonin

Gleerup, G.; Winther, Kaj

doi:10.1111/j.1365-2362.1988.tb01047.x

Cited by 30 publications

(12 citation statements)

References 16 publications

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“…Generally, in women, platelet sensitivity and aggregatory responses to 5HT remain stable in the course of aging. In men, three parameters indicate a substantial age-dependent increase in platelet activation: a decrease in EC~0 of 5HT for inducing a shape change reaction (reflecting enhanced sensitivity to 5HT), an increase in platelet aggregatory response to 5HT, and an increase in plasma 13TG [1,2]. Increased platelet aggregation in the course of aging has been confirmed in other studies where different activators (ADP, epinephrine) were used [14][15][16][17].…”

Section: Discussionmentioning

confidence: 59%

“…It has been reported that in normotensive subjects, platelet activation by 5HT and serotonin kinetics show differences related to age and sex [1,2]. Generally, in women, platelet sensitivity and aggregatory responses to 5HT remain stable in the course of aging.…”

Section: Discussionmentioning

confidence: 99%

“…However, neither receptor binding studies of alpha and beta adrenoceptors, nor studies on platelet cyclic AMP content, revealed any changes corresponding to age-related increases in platelet aggregation [2,18,19]. As serotonin amplifies platelet response to ADP and adrenaline [20], it has been suggested that the age-related increase in platelet aggregation may be the result of augmented sensitivity to 5HT [2].…”

Section: Discussionmentioning

confidence: 99%

“…In turn, platelets are activated by plasma 5HT and aggregate more easily on the injured endothelium. Platelet sensitivity to 5HT depends on the age of normotensive subjects, especially in men [1,2]. An age-dependent increase in sensitivity to 5HT (mediated by a 5HT2 receptor mechanism) and a progressive vessel injury parallel to aging (and hypertension) may plaa significant role in the development of cardiovascular thrombotic events.…”

mentioning

confidence: 99%

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Impaired uptake of 5 hydroxytryptamine platelet in essential hypertension: Clinical relevance

Fetkovska

Pletscher

Ferracin

et al. 1990

Cardiovasc Drug Ther

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Serotonin (5-hydroxytryptamine; 5HT) kinetics and platelet activation by 5HT were studied in patients with essential hypertension (n = 45), and in matched normotensive subjects (n = 45). Platelet response to 5HT and plasma beta-thromboglobulin increased with age in men, both normotensives and hypertensives. Beta-thromboglobulin and 5-hydroxyindoleacetic acid (5HIAA) excretion were higher in hypertensive men than in women. In women, no changes in platelet activity or 5HIAA excretion were found. 5HT plasma concentrations increased with blood pressure. Platelet 5HT uptake (Vmax and KM) were the lowest in hypertensive men greater than or equal to 60 years of age. This may indicate that 5HT uptake in vivo in normotensives is far below maximum (VNT much less than Vmax), whereas in hypertensive men it may be close to maximum (VHT approximately Vmax). This could reflect significantly higher 5HT plasma concentrations in vivo hypertensives than in normotensives. The reduced uptake (which was found only in hypertensive men) may indicate an insufficient compensation of the enhanced 5HT release from aggregating platelets in older men, in whom platelet activity is enhanced in vivo. It is concluded that the defect in platelet 5HT uptake in hypertensives--along with the enhanced platelet aggregation--may contribute to a critical increase in 5HT plasma concentrations locally. An increase in 5HT concentrations leads to biochemical changes (higher 5HIAA excretion) as well as to an enhanced stimulation by 5HT. This may be of clinical relevance especially in older men, in whom 5HT2-receptor mediated responses are enhanced.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Impaired uptake of 5 hydroxytryptamine platelet in essential hypertension: Clinical relevance

Fetkovska

Pletscher

Ferracin

et al. 1990

Cardiovasc Drug Ther

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“…8.7% of ticlopidine-treated patients were found to be non-responders [21]. Very few data could be found on the association between platelet aggregability, the efficiency of antiplatelet regimens and aging [7,15,20], in spite of the fact that elderly patients are known to be at an increased risk of cardio-and cerebrovascular events [1]. In a study of 3230 individuals without evidence of cardiovascular disease Tofler et al found that fibrinogen, von Willebrand factor and measures of impaired fibrinolytic potential as plasminogen activator inhibitor and tissue plasminogen activator antigens were significantly associated with advancing age indicative of a prothrombotic state [25].…”

Section: Discussionmentioning

confidence: 99%

Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients

Koltai

Fehér

Kenyeres

et al. 2008

Clinical Hemorheology and Microcirculation

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In our present study we investigated the association between platelet aggregation in patients treated with the most widely used antiplatelet agents (100 and 300-325 mg acetylsalicylic acid (ASA), 75 mg clopidogrel, 500 mg ticlopidine and the combination of 100 mg aspirin and 75 mg clopidogrel), fibrinogen levels and aging. Between 2001 and 2005 we measured in vitro platelet aggregation in 5026 vascular patients according to the method of Born. Platelet aggregation was tested with 5 and 10 µM adenosine-diphosphate, 2 µg/ml collagen and 10 µM epinephrine stimulants. Fibrinogen level was simultaneously measured in a subgroup of 3243 patients. The subjects were divided by age into decades. Platelet aggregation increased significantly with advancing age in the case of 100 and 300-325 mg ASA-treated patients (p < 0.001). In aspirin-treated patients also fibrinogen levels increased with aging (p < 0.001). There was no association between platelet aggregation or fibrinogen levels and aging either in patients treated with 75 mg clopidogrel or with 500 mg ticlopidine. Thienopyridine-treated patients exhibited significantly lower fibrinogen levels than ASA-treated individuals (p < 0.001). Our results suggest that advancing age is associated with elevated platelet aggregability in widely used antiplatelet regimens that might contribute to higher risk of cardiovascular events in the elderly.

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Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists

Gleerup

Persson

Hedner

et al. 1993

Eur J Clin Pharmacol

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The 5-HT2-receptor antagonist ketanserin (20-40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r = 0.24; P = 0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n = 12), the ex vivo aggregation to serotonin (10(-6) M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5-HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension.

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The effect of ageing on human platelet sensitivity to serotonin

Cited by 30 publications

References 16 publications

Impaired uptake of 5 hydroxytryptamine platelet in essential hypertension: Clinical relevance

Impaired uptake of 5 hydroxytryptamine platelet in essential hypertension: Clinical relevance

Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients

Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists

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