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To investigate possible alterations in 5-hydroxytryptamine (5HT) kinetics and sensitivity of blood platelets in patients with essential hypertension, 45 essential hypertensive patients and 45 normotensive healthy subjects matched in pairs for age, sex, and smoking status were compared. There were 18 women and 27 men in each group, ranging from 30 to 73 years of age. Results of essential hypertensive patients differed in several ways from those of normotensive subjects. In essential hypertensive patients, maximal 5HT uptake velocity (V^) decreased with increasing blood pressure and age and was reduced the most in older men. V^, was positively related to the EC M of 5HT for inducing a shape change reaction. In essential hypertensive patients, both V,^ of 5HT uptake and the EC* of 5HT for shape change showed positive correlations with the 5HT content in platelets; the former relation was different between the essential hypertensive and normotensive groups (F=5.53; p=0.02). These results indicate reduced uptake of 5HT by blood platelets and suggest enhanced 5HT plasma concentrations in local areas, especially vascular lesions in essential hypertensive patients. Increased periplatelet concentrations of 5HT may lead to preactivatlon of platelets and possibly stimulation of vascular smooth muscle via their 5HTj-receptors. These changes are likely to be involved in the pathogenesis of increased thromboembolic complications in essential hypertensive patients, particularly in older men. {Hypertension 1990;15:267-273) B lood platelets have a specific uptake mechanism for 5-hydroxytryptamine (5HT) (serotonin) at the plasma membrane, intracellular amine storage organelles (dense bodies), and an amine metabolizing enzyme (monoamine oxidase) as well as 5HT 2 -receptors. Stimulation of the latter causes platelet activation, rise of intracellular messengers (e.g., inositoltrisphosphate and calcium) leading to shape change reaction and eventually aggregation. In normotensive (NT) healthy subjects, platelet activation by 5HT and 5HT kinetics has been shown to depend on age and sex.1 The observed agedependent increase in platelet reactivity to 5HT in healthy men tallies with their higher cardiovascular thromboembolic complication rates. Enhanced 5HT-stimulated vasoconstriction, including that induced via endothelium-derived contracting factors, increased platelet aggregation are likely to contribute to the development of high blood pressure as well as to the greater thromboembolic risk of essential hypertensive (EHT) patients.So far, results of platelet studies in EHT patients are inconsistent. Usually, two or three functions were measured, but 5HT kinetics and platelet responses were not assessed in a comprehensive way. Thus, in EHT patients 5HT uptake 5 " 8 and 5HT content in platelets were found to be decreased, 7 -9 -10 and the release of 5HT was shown to be increased in some studies. 10- 12 Other investigations showed no statistically significant differences between EHT patients and NT subjects relative to 5HT uptake 13 -14 or...

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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