title: Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men.
abstract: BACKGROUND
  Mental stress reliably induces increases in salivary alpha amylase (sAA), a suggested surrogate marker for sympathetic nervous system (SNS) reactivity. While stress-induced sAA increases correlate with norepinephrine (NE) secretion, a potential mediating role of noradrenergic mechanisms remains unclear. In this study, we investigated for the first time in humans whether a NE-stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in sAA.
  
  
  METHODS
  In a single-blind placebo-controlled within-subjects design, 21 healthy men (29-66 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 (5 μg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2-adrenergic receptors (trial-3). Saliva samples were collected immediately before, during, and several times after substance infusion in addition to blood pressure and heart rate readings.
  
  
  RESULTS
  Experimental trials significantly differed in sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic-blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective phentolamine application was verified by blood pressure and heart rate infusion reactivity. Salivary cortisol was not affected by NE, either with or without alpha-adrenergic-blockade.
  
  
  CONCLUSIONS
  We found that NE-infusion stimulates sAA secretion, regardless of co-administered non-selective alpha-adrenergic blockade by phentolamine, suggesting that the mechanism underlying stress-induced sAA increases may involve NE.
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuebler
authors.affiliation: Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: von Känel
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland; Department of Clinical Psychology and Psychotherapy, University of Basel, Basel, Switzerland.
authors.forename: Nadja
authors.initials: N
authors.lastname: Heimgartner
authors.affiliation: Biological and Health Psychology, University of Bern, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Zuccarella-Hackl
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Guido
authors.initials: G
authors.lastname: Stirnimann
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ehlert
authors.affiliation: Biological and Health Psychology, University of Bern, Bern, Switzerland. Electronic address: petra.wirtz@psy.unibe.ch.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Wirtz
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D012463:Saliva / Q000378:metabolism; D055291:Salivary alpha-Amylases / Q000378:metabolism*; D016037:Single-Blind Method
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015415:Biomarkers; D055291:Salivary alpha-Amylases; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine
keywords: Alpha amylase; Alpha-adrenergic blocker; Cortisol; Human; Norepinephrine infusion; Phentolamine; Saliva; Stress