Norepinephrine infusion without but not with alpha-adrenergic blockade by phentolamine increases coagulation parameter levels in healthy men

Abstract

Background: Mental stress induces reliable increases in coagulation parameters including fibrinogen or D-dimer, but underlying mechanisms are not fully understood. While stress-induced D-dimer increases correlate with norepinephrine (NE) secretion, a potential role of noradrenergic mechanisms remains unclear. Here, we investigated in humans, whether a NE-stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in different coagulation parameters.Methods: In a single-blind placebo-controlled within-subjects design, 18 healthy men (33–64 years) took part in three different experimental trials varying in terms of substance infusion with a 1-min first infusion followed by a 15-min second infusion: saline-infusion (trial-1), NE infusion (5microg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2-adrenergic receptors (trial-3). Blood samples were collected immediately before, and several times after substance infusion to measure fibrinogen, FVIII:C, and D-dimer.Results: As compared to placebo-infusion (trial-1), NE-infusion without alpha-adrenergic blockade (trial-2) induced higher fibrinogen and D-dimer reactivity (p's < 009). Alpha-adrenergic blockade (trial-3) reduced coagulation parameter reactivity to NE-infusion: trial-3 did not significantly differ from both other trials (p's > 09).Conclusions: We found that NE-infusion stimulates coagulation activity and that this stimulation was in part inhibited by non-selective alpha-adrenergic blockade by phentolamine. This suggests that the mechanisms underlying stress-induced coagulation activity increases may involve NE and alpha-adrenergic receptors.