Endothelin Receptor Blockade Blunts the Pressor Response to Acute Stress in Obese Men and Women

2021 ◽  
Author(s):  
Cassandra C. Derella ◽  
Anson M. Blanks ◽  
Xiaoling Wang ◽  
Matthew A. Tucker ◽  
Chase Horsager ◽  
...  
Keyword(s):  
Acute Stress ◽  
Pressor Response ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Normal Weight ◽  
Endothelin Receptor ◽  
Treatment Results ◽  
Endothelin 1 ◽  
Endothelin System ◽  
The Impact

Obesity is associated with dysregulation of the endothelin system. In obese individuals, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1. The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese individuals is unknown. Objective: To test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared to normal weight individuals. Methods: 40 participants [Normal weight (NW): n=20, BMI: 21.7 ± 2.4 kg/m2 & Overweight/obese (OB): n=20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. Results: The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (p=0.039) in the OB group, compared to the NW group (OB: 28±12 vs LN: 34±15 mm Hg). Conclusions: These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.

scholarly journals The Importance of Adrenocortical Glucocorticoids for Adrenomedullary and Physiological Response to Stress: A Study in Isolated Glucocorticoid Deficiency

2001 ◽  
Vol 86 (12) ◽  
pp. 5920-5924 ◽  
Author(s):  
Nehama Zuckerman-Levin ◽  
Dov Tiosano ◽  
Graeme Eisenhofer ◽  
Stefan Bornstein ◽  
Ze’ev Hochberg
Keyword(s):  
Physiological Response ◽  
Acute Stress ◽  
Pressor Response ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Mild Stress ◽  
Compensatory Response ◽  
Response To Stress ◽  
Glucocorticoid Deficiency ◽  
Response To Exercise

Glucocorticoids are required for the normal functioning of chromaffin cells and their capacity to produce epinephrine. This was modeled in a unique clinical syndrome of isolated glucocorticoid deficiency due to unresponsiveness to ACTH. The working hypotheses were that in patients with isolated glucocorticoid deficiency, adrenomedullary epinephrine would be suppressed despite replacement therapy; that norepinephrine might show a compensatory response; and that the physiological response to stress would reflect these changes. Toward these hypotheses, patients with ACTH unresponsiveness on glucocorticoid replacement were subjected to three levels of acute stress: assumption of upright posture, cold pressor, and exercise. Their catecholamine and physiological response were monitored. Patients with isolated glucocorticoid deficiency of this study had severe adrenomedullary dysfunction, characterized by a minimal resting production of epinephrine (6 ± 2 pg/ml compared with 64 ± 22 pg/ml of the controls) and a minimal response to stress. A slight compensatory increase of norepinephrine was found in response to cold pressor test (754 ± 200 pg/ml compared with 431 ± 73 pg/ml of the control). The physiological response is characterized by low systolic blood pressure and high pulse rate in rest and mild stress and in a pressor response to exercise (diastolic 87 ± 5 mm Hg, compared with 73 ± 2 mm Hg of the control). It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response. The implications of the pressor response to exercise, the declining pulse pressure, and the increased pulse response insinuate a lower physical fitness in patients with adrenal insufficiency.

scholarly journals Abnormal sympathetic neural recruitment patterns and hemodynamic responses to cold pressor test in women with posttraumatic stress disorder

2020 ◽  
Vol 318 (5) ◽  
pp. H1198-H1207 ◽  
Author(s):  
Jeung-Ki Yoo ◽  
Mark B. Badrov ◽  
Mu Huang ◽  
Ryan A. Bain ◽  
Raymond P. Dorn ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Pressor Response ◽  
Muscle Sympathetic Nerve Activity ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Pressor Test ◽  
Activity Burst ◽  
Circulatory Control

The novel findings of the present study are that women with posttraumatic stress disorder (PTSD) have an augmented pressor response to the sympathoexcitatory stimulus of a cold pressor test (CPT) compared with healthy control subjects. Although integrated muscle sympathetic nerve activity burst responses were not significantly different between groups, total sympathetic action potential discharge in response to the CPT was markedly elevated in women with PTSD exhibiting increased firing of low-threshold axons as well as the recruitment of latent subpopulations of larger-sized axons that are otherwise silent at baseline. Aberrant autonomic circulatory control in response to sympathoexcitatory stimulus may in part explain the propensity toward developing hypertension and cardiovascular disease in this population.

In vivo evidence for endothelin-1-mediated attenuation of α1-adrenergic stimulation

2006 ◽  
Vol 290 (3) ◽  
pp. H1251-H1258 ◽  
Author(s):  
Gerard D’Angelo ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Acute Stress ◽  
Pressor Response ◽  
Area Under The Curve ◽  
Receptor Activation ◽  
Plasma Norepinephrine ◽  
Adrenergic Stimulation ◽  
Endothelin 1 ◽  
Air Jet ◽  
Before And After

Experiments were designed to determine the influence of endothelin A (ETA) receptors on the pressor response to acute environmental stress in Dahl salt-resistant (DR) and Dahl-sensitive (DS) rats. Mean arterial pressure (MAP) was chronically monitored by telemetry before and after treatment with the selective ETA receptor antagonist ABT-627. Rats were restrained and subjected to pulsatile air jet stress (3 min). In untreated animals, the total pressor response (area under the curve) to acute stress was not different between DR vs. DS rats (8.1 ± 1.7 vs. 15.6 ± 2.6 mmHg × 3 min, P = 0.10). Conversely, treatment with ABT-627 potentiated the total pressor response only in DR rats (36.3 ± 6.2 vs. 22.6 ± 5.9 mmHg × 3 min, DR vs. DS, P < 0.05). Treatment with ABT-627 allowed greater responses in anesthetized DR rats to exogenous phenylephrine (1–4 μg/kg) during ganglionic blockade ( P < 0.05) and produced a significant increase in plasma norepinephrine at baseline and during stress in conscious DR rats compared with untreated animals ( P < 0.05). ETA receptor blockade had no effect on these responses in DS rats. Our results suggest that endothelin-1 can inhibit α-adrenergic-mediated effects in DR, but not DS rats, consistent with the hypothesis that ETA receptor activation functions to reduce sympathetic nerve activity and responses in vascular smooth muscle to sympathetic stimulation.

scholarly journals Microneurography and sympathetic nerve activity: a decade-by-decade journey across 50 years

2019 ◽  
Vol 121 (4) ◽  
pp. 1183-1194 ◽  
Author(s):  
Jason R. Carter
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Lower Body Negative Pressure ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
The Past ◽  
Thomson Reuters ◽  
The Impact

The technique of microneurography has advanced the field of neuroscience for the past 50 years. While there have been a number of reviews on microneurography, this paper takes an objective approach to exploring the impact of microneurography studies. Briefly, Web of Science (Thomson Reuters) was used to identify the highest citation articles over the past 50 years, and key findings are presented in a decade-by-decade highlight. This includes the establishment of microneurography in the 1960s, the acceleration of the technique by Gunnar Wallin in the 1970s, the international collaborations of the 1980s and 1990s, and finally the highest impact studies from 2000 to present. This journey through 50 years of microneurographic research related to peripheral sympathetic nerve activity includes a historical context for several of the laboratory interventions commonly used today (e.g., cold pressor test, mental stress, lower body negative pressure, isometric handgrip, etc.) and how these interventions and experimental approaches have advanced our knowledge of cardiovascular, cardiometabolic, and other human diseases and conditions.

scholarly journals Impact of age and sex on neural cardiovascular responsiveness to cold pressor test in humans

2020 ◽  
Vol 319 (3) ◽  
pp. R288-R295
Author(s):  
M. L. Keller-Ross ◽  
H. A. Cunningham ◽  
J. R. Carter
Keyword(s):  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Pressor Test ◽  
Initial Rise ◽  
Group Time ◽  
The Impact ◽  
Finger Plethysmography ◽  
Age And Sex

Prior longitudinal work suggests that blood pressure (BP) reactivity to the cold pressor test (CPT) helps predict hypertension; yet the impact of age and sex on hemodynamic and neural responsiveness to CPT remains equivocal. Forty-three young (21 ± 1yr, means ± SE) men (YM, n = 20) and women (YW, n = 23) and 16 older (60 ± 1yr) men (OM, n = 9) and women (OW, n = 7) participated in an experimental visit where continuous BP (finger plethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded during a 3- to 5-min baseline and 2-min CPT. Baseline mean arterial pressure (MAP) was greater in OM than in YM (92 ± 4 vs. 77 ± 1 mmHg, P < 0.01), but similar in women ( P = 0.12). Baseline MSNA incidence was greater in OM [69 ± 6 bursts/100 heartbeats (hb)] than in OW (44 ± 7 bursts/100 hb, P = 0.02) and lower in young adults (YM: 17 ± 3 vs. YW: 16 ± 2 bursts/100 hb, P < 0.01), but similar across the sexes ( P = 0.83). However, when exposed to the CPT, MSNA increased more rapidly in OW (Δ43 ± 6 bursts/100 hb; group × time, P = 0.01) compared with OM (Δ15 ± 3 bursts/100 hb) but was not different between YW (Δ30 ± 3 bursts/100 hb) and YM (Δ33 ± 4 bursts/100 hb, P = 1.0). There were no differences in MAP with CPT between groups (group × time, P = 0.33). These findings suggest that OW demonstrate a more rapid initial rise in MSNA responsiveness to a CPT compared with OM. This greater sympathetic reactivity in OW may be a contributing mechanism to the increased hypertension risk in postmenopausal women.

scholarly journals The Influence of Examiner Gender on Responses to Tonic Heat Pain Assessments: A Preliminary Investigation

2021 ◽  
Vol 2 ◽  
Author(s):  
Jessica F. McDougall ◽  
Nicole G. N. Bailey ◽  
Rohan Banga ◽  
Lukas D. Linde ◽  
John L. K. Kramer
Keyword(s):  
Preliminary Investigation ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Assessment Method ◽  
Gender Effects ◽  
Heat Pain ◽  
Sex And Gender ◽  
Pain Thresholds ◽  
Pain Ratings ◽  
The Impact

Background: The influence of examiner gender on pain reporting has been previously explored in both research and clinical settings. However, previous investigations have been limited, with the majority of studies employing single, static assessments of pain (e.g., cold pressor test, verbal pain ratings). The impact of examiner gender on both static and dynamic heat-based pain assessments is currently unknown.Methods: Thirty eight participants (20 females aged 24.1 ± 4.44, and 18 males, aged 24.8 ± 4.54) completed two identical testing sessions, randomized to a male and female examiner in a cross-over design. Pain sensitivity was examined using heat pain thresholds, verbal pain ratings to tonic heat, computerized visual analog scale (CoVAS) rating to tonic heat, and participant-controlled temperature (PCT) heat pain assessments.Results: Female participants reported higher verbal pain to tonic heat with a female examiner compared to male participants, with similar trends for CoVAS responses to tonic heat. Conversely heat pain thresholds and PCT were not significantly influenced by experimenter gender.Conclusions: Overall, verbal ratings were the most impacted by examiner gender, with temperature-based methods such as PCT and pain thresholds showing little to no examiner gender effects. While the gender of the examiner may be an important consideration in the measurement of sex and gender differences in pain research, the choice of pain assessment method may be of similar consequence.

scholarly journals A social and physical stressor increases later punishment in healthy males

2021 ◽  
Author(s):  
Yacila Isabela Deza-Araujo ◽  
Ulrike Rimmele ◽  
Lucien Gyger ◽  
Cora Aguirre ◽  
David Sander ◽  
...  
Keyword(s):  
Social Interactions ◽  
Cold Water ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Social Contexts ◽  
Control Procedure ◽  
Water Test ◽  
Individual Variables ◽  
The Impact

Existing literature suggests that stress in early life can influence or trigger later aggressive and punishment behaviors during social interactions. However, only a few human studies have addressed this link in controlled experimental settings. Here, we assessed the impact of biological and behavioral markers of stress on economic and social interactions in healthy men using a between-group design. The Socially Evaluated Cold Pressor Test (i.e., supervised hand immersion into cold water) was applied to one group of participants (n = 19), while a second group underwent the Warm Water Test (n = 21). After the stressor or control procedure, all participants played the Inequality Game, a paradigm in which they could engage in punishment, cooperative, or aggressive behaviors towards a fair and an unfair counterpart player. Compared to the control condition, participants in the stress condition engaged in more punishment behaviors towards the unfair player and less cooperative behaviors towards both players. Critically, higher levels of cortisol in the stress group were associated with more punishment behaviors towards the unfair player. In contrast, aggressive behavior did not differ between participants in the stress vs. control condition. Overall, our findings showed that situationally induced stress might facilitate punishment behaviors in provoking situations. Further research should elucidate the role of inter-individual variables that may encourage or prevent stress-related punishment in social contexts.

Sign in / Sign up

Export Citation Format

Share Document