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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 (Vmax) decreased with increasing blood pressure and age and was reduced the most in older men. Vmax was positively related to the EC50 of 5HT for inducing a shape change reaction. In essential hypertensive patients, both Vmax of 5HT uptake and the EC50 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 preactivation of platelets and possibly stimulation of vascular smooth muscle via their 5HT2-receptors. These changes are likely to be involved in the pathogenesis of increased thromboembolic complications in essential hypertensive patients, particularly in older men.

Platelet shape change and aggregation as well as serotonin (5-hydroxytryptamine; 5HT) content in platelets, spontaneous release of 5HT, 5HT plasma levels, urinary excretion of 5-hydroxyindoleacetic acid (5HIAA) and plasma beta-thromboglobulin (beta-TG) were investigated in 45 healthy subjects (27 men, 18 women). Platelets from women were more susceptible to aggregation (both by 5HT and ADP) than platelets from men. However, in men, 5HT-induced shape change and aggregation as well as plasma beta-TG concentration increased with age. In men, 5HT-induced platelet aggregation correlated positively with 5HT plasma levels. An inverse relationship was found in men between platelet number on the one hand and platelet 5HT content, 5HT release, 5HT plasma levels and urinary 5HIAA excretion rates on the other hand. In all subjects 5HT-induced platelet aggregation correlated negatively with platelet number. These results indicate that age and gender must be considered in designing clinical studies on 5HT and in evaluating human platelet 5HT kinetics. The platelet number seems to be related to 5HT kinetics of platelets and their reaction to 5HT in men. An age-dependent change in the reactivity of platelets to 5HT (rather than their absolute 5HT sensitivity) may contribute to the enhanced platelet turnover and higher incidence of cardiac events in older men.