Prothrombotic response to norepinephrine infusion, mimicking norepinephrine stress-reactivity effects, is partly mediated by α-adrenergic mechanisms

Abstract

BackgroundStress-induced prothrombotic changes are mediated by the sympathetic nervous system and critically involved in mental triggering of acute coronary syndromes, but the underlying psychobiology is not fully understood. We tested the hypothesis that a norepinephrine (NE) infusion to mimic effects of stress-induced NE release on blood coagulation elicits prothrombotic changes and examined to what extent these would be mediated by an alpha-adrenergic mechanism.Methods and resultsIn a single-blind placebo-controlled within-subjects design, 24 middle-aged, non-smoking, non-obese and normotensive men participated in three experimental trials with an interval between one and two weeks. Each trial applied two sequential infusions of 1 and 15 min duration with varying substances [i.e., saline as placebo, the non-specific α-blocker phentolamine (2.5 mg/min), and NE (5 μg/min)]: trial 1=saline + saline; trial 2=saline + NE, and trial 3=phentolamine + NE. Plasma levels of clotting factor VIII activity (FVIII:C), fibrinogen, and D-dimer were assessed from blood samples collected immediately before and 1 min and 20 min after infusion procedures. Compared to saline + saline, saline + NE induced increases over time in FVIII:C, fibrinogen, and D-dimer levels. With phentolamine + NE, fibrinogen levels remained increased compared to saline + saline, but changes in FVIII:C and D-dimer levels were no more different. Coagulation changes did not differ between saline + NE and phentolamine + NE.ConclusionsNE infusion activates blood coagulation. The resulting prothrombotic state could be one psychobiological mechanism underlying mental triggering of acute coronary syndromes. Blockade of α-adrenergic receptors partly attenuated NE effects on coagulation and could be implied to have preventive potential in susceptible individuals.