Elsevier

Psychoneuroendocrinology

Volume 31, Issue 1, January 2006, Pages 137-141
Psychoneuroendocrinology

Short Communication
Salivary alpha amylase as marker for adrenergic activity during stress: Effect of betablockade

https://doi.org/10.1016/j.psyneuen.2005.05.012Get rights and content

Summary

Free salivary cortisol is an established non-invasive marker of hypothalamus pituitary adrenal (HPA) axis activity. In contrast, such a well-characterized salivary marker for activity of the sympatho-adrenal medullar (SAM) system is still missing. As one potential candidate salivary alpha amylase (sAA) has been suggested. In humans increases in sAA levels have been observed in response to physiological and psychological stress. The present study aimed at exploring the effects of a pharmacological manipulation (betablockade) on sAA in the context of a stressful fMRI experiment on emotional information processing. Thirty young healthy subjects participated in a double blind group comparison study and received 80 mg of the betablocker (BB) propranolol or a placebo (PL). Salivary samples were obtained before and 90 min (pre-scan) and 135 min (post-scan) after drug application. In addition heart rate and blood pressure were assessed. During rest a significant drug by time interaction was observed, lowering sAA levels as well as heart rate and systolic blood pressure in the betablocker treatment group. During the scanning procedure, in which participants were confronted with highly negative emotional pictures, the significant increase in sAA levels in the PL group compared to the BB group persisted. No additional change was noticed in heart rate or blood pressure during scanning in the PL or BB group. The current pharmacological study in the human provides direct evidence for the sensitivity of sAA to changes in adrenergic activation, specifically in reaction to psychological stress.

Introduction

The use of salivary sampling as a noninvasive tool for the assessment of free cortisol and therewith as a marker for activity of the hypothalamic pituitary adrenal (HPA) axis is well established in human stress research (Kirschbaum and Hellhammer, 1994). A corresponding relatively easy to obtain marker for the sympatho-adrenal medullar activity is still missing. Direct measurements of adrenaline and noradrenaline out of saliva seem not to reflect SAM activity (e.g. Schwab et al., 1992).

In this paper we will refer to (nor)adrenaline1 as transmitter released by the sympathetic nerve endings as well as the peripherally acting hormones released by the adrenal medulla. The salivary gland and glandular duct cells as well as the vascular bed of the salivary glands are abundantly provided with beta-adrenoceptors (Nederfors and Dahlof, 1992). Adrenaline affects the activity of the parotid salivary glands also via non-innervated beta-receptors, that are therefore responsive to hormonal actions (Lovallo and Thomas, 2000).

Salivary alpha amylase (sAA) levels have been suggested as a potential indirect marker for SAM activity but additional research in this area is clearly warranted. Animal studies have suggested that sAA is secreted after beta-adrenergic stimulation (Gallacher and Petersen, 1983). Other studies found that the result of infusion of alpha- and beta-adrenergic antagonists as well as noradrenaline and isoproterenol showed that secretion of salivary amylase is predominantly mediated by stimulation of beta-adrenergic receptors (Skov Olsen et al., 1988). In humans sAA levels have been reported to rise in response to physical stress (Gilman et al., 1979, Chatterton et al., 1996) as well as to psychological stressors (Bosch et al., 1996, Chatterton et al., 1996, Nater et al., 2005). Moreover, one study reported that sAA levels were significantly associated with noradrenaline levels measured out of plasma samples (Chatterton et al., 1996). They conclude that salivary alpha-amylase concentrations are predictive of plasma catecholamine levels under a variety of stressful conditions.

An alternative and potentially more direct assessment on the impact of changes in adrenergic activity on sAA levels could be achieved by using beta-receptor agonists or antagonists to further validate the usefulness of sAA as an adrenergic marker. Indeed an early and very small pilot study (n=5) observed that 30 mg of the betablocker propranolol reduced sAA levels in some of the subjects (Speirs et al., 1974). In a series of experiments Nederfors (Nederfors and Dahlof, 1992, Nederfors et al., 1994, Nederfors, 1996) studied the effects of beta-adrenoceptor antagonists on saliva flow rate and composition. This was evaluated both in healthy volunteers and in hypertensive patients. The effects of 1 week of treatment with the non-selective (propranolol, 80 mg) and the beta 1-selective (atenolol, 50 mg) adrenoceptor antagonists were compared with that of placebo in three different clinical trials. Salivary composition but not saliva flow rates were affected by the beta-adrenoceptor antagonists (Nederfors, 1996).

The potential of alpha amylase as a salivary marker of adrenergic activity could be of substantial interest for human stress research since it would allow the parallel investigation of the two major neuro-endocrine stress systems with salivary samples (Chatterton et al., 1996).

The goal of the present placebo controlled double blind study therefore was to investigate the effects of a pharmacological manipulation of the SAM system when participants underwent a stressful procedure (watching highly negative emotional pictures in a scanner). For this purpose we used a non-selective betablocker (80 mg propranolol) to explore its effect on sAA levels and on two additional well-established markers of adrenergic activity (heart rate and blood pressure). We hypothesized first that betablockade would lower all markers of the SAM system during rest. Secondly, if increased sAA levels are a sensitive indicator of increased adrenergic activation, then the experimental procedure would have to provoke rising sAA levels under placebo condition, but less so under betablockade.

Section snippets

Subjects

Thirty right-handed subjects (15 males, 15 females; mean age 20.93±2.38, ranging from 18 to 28 years) without medical or psychiatric history were selected after an introduction interview, where they were screened with the Symptom Check List (SCL-90) (mean score=104.03±9.48) and a biographic questionnaire. Subjects were students of the University of Amsterdam and received course credit for participation. The Medical Ethical Committee of the VU Medical Center (VUMC) approved the experiment and

Effects of betablockade

At baseline (t0) drug groups were comparable with respect to sAA, HR, SYS and DIAS values (all p>0.10). Then the drug (BB/PL) ×time (3) interaction effect on amylase was analysed. A significant interaction effect of drug with time (F(2, 25)=11.76, p<0.001) was found indicating that betablockade lowered the amylase level compared to placebo (Fig. 1a). Simple contrasts showed that sAA levels decreased significantly between t0 and t1 in the BB group, whereas sAA levels increased in the PL group (F

Discussion

The main finding of the present study is that treatment with the betablocker propranolol blocked the stress induced increase of sAA levels observed in the placebo group. This observation extends previous work in animals (Gallacher and Petersen, 1983) and humans (Speirs et al., 1974, Nederfors and Dahlof, 1992, Nederfors et al., 1994, Nederfors, 1996) that showed that betablockade lowered sAA levels studied in a resting condition. Our pharmacological experiment therefore strongly supports the

Acknowledgements

This study was supported by a grant from the Foundation for Behavioural and Educational Sciences of the Netherlands Organization of Scientific Research (NWO) and the CSC Amsterdam.

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