Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets.
We measured alpha 2-adrenoreceptor density as well as affinity for and sensitivity to agonist on intact platelets of normotensive and hypertensive subjects before and after physiological increases in plasma catecholamines. In normotensives, posture-induced rises in plasma catecholamines correlated with reduced alpha 2-adrenoreceptor agonist affinity and fewer high affinity state receptors. Platelet aggregation and inhibition of adenylate cyclase by L-epinephrine also was reduced. Hypertensive subjects had similar rises in plasma catecholamines with upright posture, but showed no change in receptor affinity or sensitivity. No change in platelet alpha 2-adrenoreceptor number occurred in these studies. In vitro incubation with L-epinephrine revealed that platelets from hypertensives had slower desensitization than those from normotensives. Binding studies at different temperatures and with varying sodium concentrations found no thermodynamic or sodium-dependent differences between normotensive and hypertensive groups. These studies demonstrate that platelets from hypertensive subjects exhibit a defect in the ability of physiological concentrations of agonist to desensitize the alpha 2-adrenoreceptor.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D011187:Posture; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013816:Thermodynamics; D015016:Yohimbine / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000244:Adenosine Diphosphate; D012964:Sodium; D000527:Alprostadil; D004837:Epinephrine