Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation

2008 ◽  
Vol 104 (3) ◽  
pp. 756-760 ◽  
Author(s):  
Sebastian Strempel ◽  
Christoph Schroeder ◽  
Ruth Hemmersbach ◽  
Andrea Boese ◽  
Jens Tank ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Activity ◽  
Norepinephrine Transporter ◽  
Standing Position ◽  
Vertical Acceleration ◽  
Short Term ◽  
Double Blind ◽  
Gravitational Stress ◽  
Head Up Tilt

Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 ± 1 yr, body mass index 24 ± 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt

2003 ◽  
Vol 95 (1) ◽  
pp. 159-166 ◽  
Author(s):  
Amy L. Hakeman ◽  
Jami L. Shepard ◽  
Don D. Sheriff
Keyword(s):  
Blood Pressure ◽  
Inferior Vena Cava ◽  
Inferior Vena ◽  
Vena Cava ◽  
Vascular Occlusion ◽  
Vertical Acceleration ◽  
Sprague Dawley ◽  
Regulatory Systems ◽  
Gravitational Stress ◽  
Head Up Tilt

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the “push-pull effect.” The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90° head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90° head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 ± 1.3, -23 ± 0.7, and -28 ± 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences ( P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.

Short-term variability of blood pressure and heart rate in Guillain-Barreá syndrome without respiratory failure

1999 ◽  
Vol 96 (6) ◽  
pp. 613-621 ◽  
Author(s):  
Djillali ANNANE ◽  
Véronique BAUDRIE ◽  
Anne-Sophie BLANC ◽  
Dominique LAUDE ◽  
Jean-Claude RAPHAËL ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Respiratory Failure ◽  
Plasma Noradrenaline ◽  
Heart Period ◽  
Short Term ◽  
Heart Period Variability ◽  
Period Variability ◽  
Head Up Tilt ◽  
Short Term Variability

The effect of Guillain-Barré syndrome (GBS) on the short-term variability of blood pressure and heart rate was evaluated in six patients presenting with a moderate form of the syndrome, i.e. unable to stand up unaided and without respiratory failure, at the height of the disease and during recovery. The patients were compared with six age-matched healthy volunteers. During the acute phase of the syndrome, GBS patients exhibited a significant heart rate elevation (+26 beats/min compared with healthy subjects), but the acceleratory response to atropine, or to 60 ° head-up tilt, was maintained. Resting plasma noradrenaline levels were high in acute GBS, but the secretory response to tilt was preserved. Desensitization to noradrenaline was observed in acute GBS with a reduced pressor action of this α-adrenoceptor agonist. Blood pressure levels were normal and head-up tilt did not induce orthostatic hypotension in this moderate form of GBS. Power spectral analysis demonstrated marked alterations in cardiovascular variability. The overall heart period variability was markedly reduced with the reduction predominantly in the high-frequency (respiratory) range (-73%). The low-frequency component of heart period variability was also reduced (-54%). This cardiovascular profile of moderate GBS at the height of the disease could result from a demyelination of the reflex loop controlling respiratory oscillations in heart rate and from a desensitization of the arterial tree to an elevated plasma noradrenaline. Sympathetic nervous activation may contribute to the high resting heart rate in acute GBS.

Hemodynamic and Electrocardiographic Effects of Short-Term Ginkgo Biloba

2003 ◽  
Vol 37 (3) ◽  
pp. 345-349 ◽  
Author(s):  
James S Kalus ◽  
Alexandria A Piotrowski ◽  
Christopher R Fortier ◽  
Xinhcun Liu ◽  
Jeffrey Kluger ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Ginkgo Biloba ◽  
Study Drug ◽  
P Wave ◽  
Short Term ◽  
Double Blind ◽  
Electrocardiographic Parameters ◽  
Time Point

OBJECTIVE: To evaluate the immediate and short-term hemodynamic and electrocardiographic effects of Ginkgo biloba (ginkgo). METHODS: Healthy volunteers were randomized to receive ginkgo 120 mg or placebo twice daily for 7 days in this prospective, double blind trial. After at least a 7-day washout period, subjects were crossed over to an additional 7 days of alternate therapy. Blood pressure, heart rate, and 12-lead electrocardiograms were evaluated immediately before (baseline), and at 1, 3, and 5 hours after observed ingestion of study drug on days 1 and 7 of therapy. Electrocardiographic parameters (P wave and QRS complex duration; PR, QT, and QTc intervals) were measured in lead II by a blinded investigator. RESULTS: Ginkgo had no effect on any of the evaluated electrocardiographic parameters at any time point on days 1 or 7. Additionally, no changes in heart rate or systolic and diastolic blood pressure were found between the groups at any time point on any evaluative day. CONCLUSIONS: Commonly used doses of Ginkgo biloba do not have any immediate or short-term effects on blood pressure, heart rate, or electrocardiographic variables in young, healthy volunteers.

Autonomic control of vasovagal syncope

1998 ◽  
Vol 274 (6) ◽  
pp. H2110-H2115 ◽  
Author(s):  
David L. Jardine ◽  
Hamid Ikram ◽  
Christopher M. Frampton ◽  
Rachell Frethey ◽  
Sinclair I. Bennett ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Sympathetic Activity ◽  
Forearm Blood Flow ◽  
Vasovagal Syncope ◽  
Cardiac Activity ◽  
Baroreceptor Sensitivity ◽  
Head Up Tilt ◽  
Muscle Nerve

In the pathophysiological study of vasovagal syncope, the nature of the interaction between baroreceptor sensitivity (BS), sympathetic withdrawal, and parasympathetic activity has yet to be ascertained. Altered BS may predispose toward abnormal sympathetic and parasympathetic responses to orthostasis, causing hypotension that may progress to syncope if there is sympathetic withdrawal. To examine this hypothesis, we monitored blood pressure (BP), heart rate (HR), BS, forearm blood flow, and muscle nerve sympathetic activity (MNSA) continuously in 18 vasovagal patients during 60° head-up tilt, syncope, and recovery. Results were compared with those of 17 patients who were able to tolerate tilt for 45 min. During early tilt, BP was maintained in both groups by an increase in HR and MNSA from baseline ( P < 0.01), but BS decreased more in the syncopal group ( P < 0.05). At the start of presyncope (mean 2.7 ± 0.2 min before syncope and 15.2 ± 12 min after tilt), when BP fell, HR and sympathetic activity remained increased from baseline ( P< 0.01). Thereafter, BP and HR correlated directly with sympathetic activity and regressed in linear fashion until syncope ( P < 0.001), whereas BS increased to baseline. At syncope, BP, HR, and sympathetic activity fell below baseline ( P < 0.01, P < 0.05, and P < 0.01, respectively), but BS did not increase. During recovery, sympathetic activity increased to baseline and BS increased ( P < 0.05), whereas HR and BP remained low ( P < 0.01 and P < 0.05, respectively). The mechanism for the initiation of hypotension during presyncope remains unknown, but BS may contribute. Vasodilatation and bradycardia during presyncope appear to be more closely related to withdrawal of sympathetic activity than to increased parasympathetic cardiac activity.

Effect of nitric oxide synthase inhibitors on short-term appetite and food intake in humans

1999 ◽  
Vol 276 (6) ◽  
pp. R1562-R1568 ◽  
Author(s):  
Rosalie Vozzo ◽  
Gary A. Wittert ◽  
Michael Horowitz ◽  
John E. Morley ◽  
Ian M. Chapman
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Food Intake ◽  
Animal Studies ◽  
Caloric Intake ◽  
Short Term ◽  
Double Blind ◽  
Visual Analog Scales ◽  
Oxide Synthase

Animal studies suggest that nitric oxide (NO) may be a physiological regulator of appetite; NO synthase (NOS) inhibition suppresses food intake in rats, mice, and chickens. It is not known whether NO has any effect on appetite in humans. We have used N G-monomethyl-l-arginine (l-NMMA) and N G-nitro-l-arginine methyl ester (l-NAME), both competitive, nonselective inhibitors of NOS, in two separate studies to evaluate the role of NO in the short-term regulation of appetite in humans. In study I, 13 men (18–25 yr) underwent paired studies, in randomized, double-blind fashion, after an overnight fast. l-NMMA (4 mg ⋅ kg−1 ⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 40 ml/h for 1.5 h. In study II, eight men (18–26 yr) underwent three randomized, double-blind studies after an overnight fast. l-NAME (75 or 180 μg ⋅ kg−1 ⋅ h−1) or saline (0.9%) was infused intravenously at a rate of 20 ml/h for 120 min. Hunger and fullness were measured using visual analog scales; blood pressure and heart rate were monitored, and 30 min before the end of the infusion, subjects were offered a cold buffet meal. Total caloric intake and the macronutrient composition of the meal were determined. Both l-NMMA ( P = 0.052) andl-NAME ( P < 0.05; both doses) decreased heart rate, l-NMMA increased diastolic blood pressure ( P < 0.01), and l-NAME increased systolic blood pressure ( P = 0.052). Neither drug had any effect on caloric intake or sensations of hunger or fullness. Despite having significant effects on cardiovascular function in the doses used, neitherl-NMMA norl-NAME had any effect on feeding, suggesting that NO does not affect short-term appetite or food intake in humans.

Long- and Short-Term Blood Pressure and Rr-Interval Variability and Psychosomatic Distress in Chronic Fatigue Syndrome

1998 ◽  
Vol 94 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Daniel A. Duprez ◽  
Marc L. De Buyzere ◽  
Benny Drieghe ◽  
Friedl Vanhaverbeke ◽  
Youri Taes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Standing Position ◽  
Spectral Indices ◽  
Short Term ◽  
Night Time ◽  
Rr Interval ◽  
Fatigue Syndrome

1. Chronic low blood pressure has been associated with fatigue and low mood. However, in the chronic fatigue syndrome (CFS) the blood pressure (BP) and heart rate profile and their variabilities have not been characterized as yet. 2. We performed office and 24 h ambulatory BP recordings in 38 subjects (age, 34.8 ± 8.0 years) who fulfilled the Holmes criteria for CFS and in 38 healthy control subjects (age 35.6 ± 10.5 years), as well as short-term beat-to-beat BP and RR-interval recordings for 10 min in supine and standing position, and calculated spectral indices. 3. In CFS office (123 ± 19/70 ± 12 mmHg) as well as 24-h, day- and night-time blood pressure values (116 ± 11.1/71 ± 11.1, 121 ± 9.2/77 ± 8.0 and 110 ± 10.5/65 ± 9.2 mmHg respectively) were within reference limits. 4. Heart rate was consistently higher (P < 0.01) in CFS patients, based on both office (77 ± 12 compared with 68 ± 12 beats min−-1) and 24 h ambulatory recordings (77 ± 12 compared with 67 ± 15 beats min−-1). 5. In supine position, spectral indices of BP variability (total, low-frequency and high-frequency variances) were all significantly (P < 0.01) lower in CFS. In standing position the differences disappeared. Analysis of RR-interval variability could not detect major alterations in autonomic function in CFS.

Caffeine and Placebo Expectation

2007 ◽  
Vol 21 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Yunfeng Sun ◽  
Yinling Zhang ◽  
Ning He ◽  
Xufeng Liu ◽  
Danmin Miao
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sleep Deprivation ◽  
Cognitive Performance ◽  
Cognitive Functions ◽  
Cardiovascular Regulation ◽  
Double Blind ◽  
Positive Effects ◽  
Pressure Tests ◽  
Healthy Males

Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.

Reduction in Pain Sensitivity from Pharmacological Elevation of Blood Pressure in Persons with Chronically Low Blood Pressure

2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Pain Sensitivity ◽  
Pain Threshold ◽  
Pain Perception ◽  
Drug Effects ◽  
Pressure Effects ◽  
Double Blind ◽  
Low Blood Pressure ◽  
Present Trial

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

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