Role of catecholamines in platelet function: pathophysiological and clinical significance

Abstract

Platelets are involved in the pathogenesis of vascular damage in both atherosclerosis and arterial hypertension. Their reactivity in vivo is influenced by different factors, including sympathoadrenal activation, plasma levels of atherogenic lipoproteins and haemorrheological changes. In the present review, we examine the modulation of platelet function by the sympathoadrenal system and concentrate on the role of circulating catecholamines in the control of platelet responses. Human platelets exhibit both adrenergic and dopaminergic receptors that are influenced by different catecholamines. alpha(2)-Adrenoceptors of alpha(2A) subtype prevail on platelet membrane; through their stimulation, catecholamines potentiate the effects of other agonists and, at higher concentrations, initiate platelet responses, including aggregation, secretion and arachidonate pathway activation. Physiological and pathological conditions causing sympathoadrenal activation in vivo, i.e. physical activity, mental stress, insulin-induced hypoglycaemia, acute coronary ischaemia and heart failure, modify the circulating platelet populations and modulate platelet reactivity through an increase in circulating catecholamines. A sympathoadrenal hyperactivation modifies the function of circulating platelets through direct catecholamine effects, catecholamine-induced changes of haemodynamic factors and lipid pattern and inhibition of the vascular eicosanoid synthesis. The catecholamine effects on platelet function can be involved in the interplay among stress, adrenomedullary system activation and cardiovascular diseases.

Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm

“…27 Although the origin of platelet activation in CHF remains to be established, increased platelet activity might be related to elevation of cytosolic free calcium concentrations 28 and to the fact that platelets may be affected by enhanced sympathoadrenal activation and catecholamine release in CHF. 29 In the present study, the observed beneficial effects of ACE inhibitors on plasma fibrinogen and vWF levels may offer a potential explanation for the reduction in (thrombosis related) ischemic events with the use of these agents in clinical trials. 12 The precise mechanism for a reduction in plasma fibrinogen and vWF levels with ACE inhibitors in CHF remains to be established, although in the present study, the changes in plasma fibrinogen and vWF levels did not appear to be directly related to the reduction in blood pressure.…”

PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

“…The α2-adrenoceptors in platelets are coupled to Gz/Gi protein and are known to mediate aggregation by reducing the level of cyclic AMP (cAMP) and increasing intracellular Ca +2 release (12), finally leading to exposure of fibrinogen receptors (13). Next to Gi protein-mediated cAMP reduction, activation of the PI3K-mediated Akt pathway is also known to be essential to the signaling of epinephrine-induced platelet aggregation and for the potentiation of other agonists (14,15).…”

The Association Between Trait Anger and Incident Stroke Risk

“…There can be direct injury to the blood vessel walls in response to increased blood pressure and increased flow velocity and in response to an exaggerated discharge of catecholamines (eg, epinephrine and norepinephrine). 21,22 Furthermore, catecholamines can initiate other vascular and prothrombotic events that are associated with atherosclerosis such as increased platelet adhesion and aggregation, 23 vascular lipid uptake, 24 and activation of macrophages. 25 Parenthetically, in this study, the prevalence of hypertension was only slightly higher in persons in the high-anger group compared with that in the low-or moderateanger groups.…”