5-Hydroxytryptamine kinetics and activation of blood platelets in patients with essential hypertension.

Abstract

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...

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

“…On the other hand, 5HT content in platelets of normotensives correlates with platelet count. This may indicate that 5HT uptake in viva in normotensives is much lower than Vma x (VNT ,< Vmax) , whereas it may be fully saturated in hypertensives (VHT ~ Vm~), reflecting significantly higher 5HT plasma concentrations in viva in hypertensives than in normotensives [7]. The defect in platelet 5HT uptake, i.e., the reduced Vm~ may lead to a critical increase in 5HT plasma concentrations locally and, consequently, to a higher stimulation by 5HT.…”

“…It has been shown that maximal velocity of 5HT uptake (Vm~) decreases in patients with essential hypertension [3][4][5][6][7] and that the reduced uptake may lead to higher periplatelet 5HT concentrations, especially in older hypertensive men [7]. All these changes in 5HT kinetics may affect platelet sensitivity to 5HT [7]. Consequently, the aim of the present study was to define the clinical significance of the impaired 5HT uptake and platelet activation in patients with essential hypertension.…”

“…An increase in plasma 5HT concentrations is prevented by two mechanisms: a) by platelet 5HT uptake(uptake velocity increases with rising plasma 5HT concentration) and b) by 5HT metabolism by monoamine oxidase (MAO) to 5-hydroxyindoleacetic acid (5H1AA). It has been shown that maximal velocity of 5HT uptake (Vm~) decreases in patients with essential hypertension [3][4][5][6][7] and that the reduced uptake may lead to higher periplatelet 5HT concentrations, especially in older hypertensive men [7]. All these changes in 5HT kinetics may affect platelet sensitivity to 5HT [7].…”

Arterial 5-Hydroxytryptamine Transporter Function Is Impaired in Deoxycorticosterone Acetate and Nω-Nitro- l -Arginine But Not Spontaneously Hypertensive Rats

“…However, many reports showed that plasma 5-HT concentrations and arterial 5-HT receptors are changed in hypertension. In essential hypertensive humans 19 and cyclosporine-induced hypertensive rats, 20 reduced levels of platelet 5-HT and increased plasma 5-HT concentration were measured. Consistent with these reports, unpublished work from our laboratory determined that the DOCA-salt rat platelet 5-HT was reduced (ng/mL of whole blood, SHAM (D) ϭ215.6Ϯ35.4 and DOCAϭ150.4Ϯ 36.7), whereas free-circulating 5-HT concentration was increased (ng/mL whole blood, SHAM (D) ϭ5.82Ϯ1.14 and DOCAϭ28.1Ϯ11.1).…”

The love of a lifetime: 5-HT in the cardiovascular system

“…While the quantity of this 5-HT paled compared with the 5-HT made by the intestine, it is an important finding because it draws attention to two points. Part of the reason for pursuing 5-HT as a pathogenic factor in hypertension is that plasma levels of 5-HT are elevated in hypertension subjects compared with subjects with normal blood pressure (5,13). One could envision this higher level of 5-HT activating vascular receptors to promote increases in total peripheral resistance and blood pressure.…”