Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men

Psychoneuroendocrinology. 2014 Nov:49:290-8. doi: 10.1016/j.psyneuen.2014.07.023. Epub 2014 Aug 1.

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.

Keywords: Alpha amylase; Alpha-adrenergic blocker; Cortisol; Human; Norepinephrine infusion; Phentolamine; Saliva; Stress.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adult
  • Aged
  • Anxiety / chemically induced
  • Anxiety / metabolism
  • Biomarkers / metabolism
  • Blood Pressure / drug effects
  • Epinephrine / blood
  • Healthy Volunteers
  • Heart Rate / drug effects
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Norepinephrine / administration & dosage
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / pharmacology*
  • Phentolamine / pharmacology*
  • Saliva / metabolism
  • Salivary alpha-Amylases / metabolism*
  • Single-Blind Method

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Biomarkers
  • Salivary alpha-Amylases
  • Norepinephrine
  • Epinephrine
  • Phentolamine