Alpha-Adrenergic Mechanisms in the Cardiovascular Hyperreactivity to Norepinephrine-Infusion in Essential Hypertension.

Aims: Essential hypertension (EHT) is characterized by cardiovascular hyperreactivity to stress but underlying mechanism are not fully understood. Here, we investigated the role of α-adrenergic receptors (α-AR) in the cardiovascular reactivity to a norepinephrine (NE)-stress reactivity-mimicking NE-infusion in essential hypertensive individuals (HT) as compared to normotensive individuals (NT). Methods: 24 male HT and 24 male NT participated in three experimental trials on three separate days with a 1-min infusion followed by a 15-min infusion. Trials varied in infusion-substances: placebo saline (Sal)-infusions (trial-1:Sal+Sal), NE-infusion without (trial-2:Sal+NE) or with non-selective α-AR blockade by phentolamine (PHE) (trial-3:PHE+NE). NE-infusion dosage (5µg/ml/min) and duration were chosen to mimic duration and physiological effects of NE-release in reaction to established stress induction protocols. We repeatedly measured systolic (SBP) and diastolic blood pressure (DBP) as well as heart rate before, during, and after infusions. Results: SBP and DBP reactivity to the three infusion-trials differed between HT and NT (p's≤.014). HT exhibited greater BP reactivity to NE-infusion alone compared to NT (trial-2-vs-trial-1: p's≤.033). Group differences in DBP reactivity to NE disappeared with prior PHE blockade (trial-3: p=.26), while SBP reactivity differences remained (trial-3: p=.016). Heart rate reactivity to infusion-trials did not differ between HT and NT (p=.73). Conclusion: Our findings suggest a mediating role of α-AR in DBP hyperreactivity to NE-infusion in EHT. However, in SBP hyperreactivity to NE-infusion in EHT, the functioning of α-AR seems impaired suggesting that the SBP hyperreactivity in hypertension is not mediated by α-AR.

Greater than the sum of the parts: a qualitative content analysis of what constitutes a good treatment in the inpatient setting.

BACKGROUND: The evaluation of psychotherapy is guided by established concepts, such as efficacy and effectiveness, and acceptability. Although these concepts serve as valid proxies, little is known about corresponding criteria for those directly involved in this treatment. This study aimed to explore inpatients' and health professionals' definitions of a good treatment in the inpatient setting. METHODS: Fifteen semi-structured interviews were conducted in a private psychiatric clinic in Switzerland and structured by qualitative content analysis. Different subsamples of the inpatient setting (patients N = 5; psychiatrists N = 5; other health professionals N = 5) were interviewed. RESULTS: In total, 546 text passages were grouped in 10 superordinate categories and identified as relevant for the concept of a good treatment. Participants stressed patient-specific (i.e., new insights; basic attitudes), treatment-specific (i.e., therapy methods and expertise; treatment success; therapy setting), and relationship-based (i.e., communication and feedback; relationships within the clinical setting; overcoming challenges and hurdles) components that are indispensable for a good therapeutic process. Components that are related to the clinical inpatient setting (i.e., setting and organization of the clinic; code of conduct) were also highlighted. CONCLUSIONS: Patients' and health professionals' definitions of what constitutes a good treatment entails a wide array of aspects. The clinical setting is seen to offer unique components that are emphasized to have a healing effect.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension.

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p's > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

Randomized controlled evaluation of the psychophysiological effects of social support stress management in healthy women.

Considering the high and increasing prevalence of stress, approaches to mitigate stress-related biological processes become a matter of public health. Since supportive social interactions contribute substantially to mental and physical health, we set out to develop a social support stress management intervention and examined its effects on psychophysiological stress responses as well as self-reported stress in healthy women. In a parallel-group randomized controlled trial, registered in the DSRK (DRKS00017427), 53 healthy women were randomly assigned to a social support stress management or a waitlist control condition. All participants underwent a standardized psychosocial stress test where physiological and emotional stress responses were assessed by repeated measurements of cortisol, heart rate, heart rate variability and state anxiety. Also, all participants completed self-report questionnaires of perceived stress and social support at pre-intervention, post-intervention and follow-up four weeks later. Participants in the social support stress management showed a significantly attenuated integrated state anxiety response in comparison to those in the control condition, but conditions did not differ in any of the assessed physiological stress responses. The intervention significantly reduced perceived stress in comparison to the control condition, but perceived stress levels returned to baseline at follow-up. Our results indicated that the intervention had no effect on physiological responses to acute psychosocial stress, even though anxiety responses to stress were attenuated. However, the social support stress management intervention had a significant, albeit transient impact on perceived stress.

Acute Stress Improves Concentration Performance.

Acute stress can have both detrimental and beneficial effects on cognitive processing, but effects on concentration performance remain unclear. Here, we investigate the effects of acute psychosocial stress on concentration performance and possible underlying physiological and psychological mechanisms. The study sample comprised 47 healthy male participants who were randomly assigned either to a psychosocial stress situation (Trier Social Stress Test) or a neutral control task. Concentration performance was assessed using the d2 Test of Attention before and 30 min after the stress or control task. Salivary cortisol and alpha-amylase were repeatedly measured before and up to 1 hr after stress. We repeatedly assessed state anxiety using the State-Trait Anxiety Inventory and anticipatory cognitive stress appraisal using the Primary Appraisal Secondary Appraisal questionnaire. The stress group showed a significantly stronger improvement of concentration performance compared to the control group (p = .042). Concentration performance improvement was predicted by increased state anxiety (p = .020) and lower cortisol (stress) changes (p = .043). Neither changes in alpha-amylase nor cognitive stress appraisal did relate to concentration performance. Our results show improved concentration performance after acute psychosocial stress induction that was predicted by higher state anxiety increases and lower cortisol increases. This points to a potential modulating role of specific psycho-emotional and physiological factors with opposite effects.

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

BACKGROUND: Stress-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 RESULTS: In 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. CONCLUSIONS: NE 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.

The Role of Norepinephrine and α-Adrenergic Receptors in Acute Stress-Induced Changes in Granulocytes and Monocytes.

OBJECTIVE: Acute stress induces redistribution of circulating leucocytes in humans. Although effects on lymphocytes as adaptive immune cells are well understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and α-adrenergic receptors (α-ADRs) may play a mediating role. METHODS: In a stress study, we cross-sectionally tested 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1- and 15-minute duration with varying substances (saline as placebo, the nonspecific α-ADR blocker phentolamine [2.5 mg/min], and NE [5 µg/min]): trial 1 = saline+saline, trial 2 = saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10 minutes, and 30 minutes after infusion procedures. RESULTS: In the stress study, higher NE related to higher neutrophil stress changes (ß = .31, p = .045, R change = .09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60) = 43.50, p < .001, η = .69) and monocyte (F(3/60) = 18.56, p < .001, η = .48) numbers compared with saline+saline. With phentolamine+NE, neutrophil (F(3/60) = 14.41, p < .001, η = .42) and monocyte counts (F(2.23/44.6) = 4.32, p = .016, η = .18) remained increased compared with saline+saline but were lower compared with saline+NE (neutrophils: F(3/60) = 19.55, p < .001, η = .494, monocytes: F(3/60) = 2.54, p = .065, η = .11) indicating partial mediation by α-ADRs. Trials did not differ in eosinophil and basophil count reactivity. CONCLUSIONS: Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of α-ADRs.

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

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.

Stress-induced cortisol secretion impairs detection performance in x-ray baggage screening for hidden weapons by screening novices.

Aviation security strongly depends on screeners' performance in the detection of threat objects in x-ray images of passenger bags. We examined for the first time the effects of stress and stress-induced cortisol increases on detection performance of hidden weapons in an x-ray baggage screening task. We randomly assigned 48 participants either to a stress or a nonstress group. The stress group was exposed to a standardized psychosocial stress test (TSST). Before and after stress/nonstress, participants had to detect threat objects in a computer-based object recognition test (X-ray ORT). We repeatedly measured salivary cortisol and X-ray ORT performance before and after stress/nonstress. Cortisol increases in reaction to psychosocial stress induction but not to nonstress independently impaired x-ray detection performance. Our results suggest that stress-induced cortisol increases at peak reactivity impair x-ray screening performance.