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Effect of standing on neurohumoral responses and plasma volume in healthy subjects
Abstract
Upright posture leads to rapid pooling of blood in the lower extremities and shifts plasma fluid into surrounding tissues. This results in a decrease in plasma volume (PV) and in hemoconcentration. There has been no integrative evaluation of concomitant neurohumoral and PV shifts with upright posture in normal subjects. We studied 10 healthy subjects after 3 days of stable Na+and K+intake. PV was assessed by the Evans blue dye method and by changes in hematocrit. Norepinephrine (NE), NE spillover, epinephrine (Epi), vasopressin, plasma renin activity, aldosterone, osmolarity, and kidney response expressed by urine osmolality and by Na+and K+excretion of the subjects in the supine and standing postures were all measured. We found that PV fell by 13% (375 ± 35 ml plasma) over ∼14 min, after which time it remained relatively stable. There was a concomitant decrease in systolic blood pressure and an increase in heart rate that peaked at the time of maximal decrease in PV. Plasma Epi and NE increased rapidly to this point. Epi approached baseline by 20 min of standing. NE spillover increased 80% and clearance decreased 30% with 30 min of standing. The increase in plasma renin activity correlated with an increase in aldosterone. Vasopressin increased progressively, but there was no change in plasma osmolarity. The kidney response showed a significant decrease in Na+and an increase in K+excretion with upright posture. We conclude that a cascade of neurohumoral events occurs with upright posture, some of which particularly coincide with the decrease in PV. Plasma Epi levels may contribute to the increment in heart rate with maintained upright posture.
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“However, levels of norepinephrine in POTS patients can increase more than threefold, exceeding 800 pg/ml in many cases, while the increase in healthy controls after assuming an upright position is much more modest at approximately 400-500 pg/ml (36, 43).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [43]
In the citing paper
“In healthy subjects, the supine plasma norepinephrine level is approximately 200 pg/ml, and upon standing, it doubles before it plateaus after 7.5 min (43).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [43]
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Computational modeling of orthostatic intolerance for travel to Mars
van Loon, L. M., Steins, A., Schulte, K., Gruen, R. L., & Tucker, E. M. (2022) · npj Microgravity · doi:10.1038/s41526-022-00219-2 · Cited by 17
The Current Perception Thresholds Vary Between Horizontal and 70° Tilt-Up Positions
Shimoda, O., & Ikuta, Y. (2000) · Anesthesia & Analgesia · doi:10.1097/00000539-200008000-00031 · Cited by 15
Chavasiri, C., Natchaya, S., Luksanapruksa, P., Wilartratsami, S., & Chavasiri, S. (2022) · Spinal Cord Series and Cases · doi:10.1038/s41394-022-00475-0 · Cited by 12
“Second, antidiuretic hormone is secreted in extremely high concentrations in response to orthostatic hypotension [24].”
BackgroundLi, L., Li, H., He, L., Chen, H., & Li, Y. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.603957 · Cited by 13
“Some studies have shown that non-neurogenic OH was related to autonomic nervous dysfunction and decreased vascular capacity regulation (7).”
BackgroundNorepinephrine and Epinephrine Responses during Orthostatic Intolerance in Healthy Elderly Men
Gabbett, T. J., Gass, G., Gass, E., Morris, N. R., Bennett, G., & Thalib, L. (2000) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.50.59 · Cited by 11
“While considered a valid method for estimating total blood volume [22, 23], the use of height and body mass to predict blood volume should be utilized with caution as vascular volumes may also be influenced by aerobic capacity and lean body mass [34].”
Orthostatic Hypotension for People with Spinal Cord Injuries
Chao, C. Y. L., & Cheing, G. L. Y. (2008) · Hong Kong Physiotherapy Journal · doi:10.1016/s1013-7025(09)70008-9 · Cited by 10
“angiotensin system and releases epinephrine and arginine vasopressin [13,14,19,20].”
InfluentialSubclinical orthostatic pulse pressure confirms mothers' ratings of ADHD in preschoolers
Casavant, V., Chae, C., Sherwani, A., & Perlmuter, L. C. (2012) · Psychophysiology · doi:10.1111/j.1469-8986.2012.01351.x · Cited by 8
Orthostatic cardiovascular profile of subjective well-being
Davydov, D. M., & Czabak-Garbacz, R. (2016) · Biological Psychology · doi:10.1016/j.biopsycho.2016.11.014 · Cited by 9
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“The plasma volume shift from vascular space to interstitial space is also greatly enhanced in orthostasis of patients with OI.19 Several studies showed that relative excessive cardiac sympathetic activities may explain symptoms such as dyspnea, chest tightness, and tachycardia.20,21 With a similar mechanism, sympathet…”
BackgroundInfluentialTilt-table testing as a predictor of + GZ tolerance
Zawadzka-Bartczak, E., & Kopka, L. (2005) · Indian Journal of Medical Sciences · doi:10.4103/0019-5359.18964 · Cited by 9
“The same mechanisms (blood redistribution and reflex response) occurs with body position change from recumbent to erect.[7] Baroreceptor function disturbances are responsible for orthostatic hypotension (vasovagal reflex and syncope) even in clinically healthy individuals.”
BackgroundCardiovascular Autonomic Profile in Women With Premenstrual Syndrome
Koifman, R., Dayan, L., Ablin, J. N., & Jacob, G. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01384 · Cited by 9
Self-citationAssessment of autonomic dysfunction and anxiety levels in patients with mitral valve prolapse.
Orhan, A. L., Sayar, N., Nurkalem, Z., Uslu, N., Erdem, İ., Erdem, E., Erer, H. B., Soylu, Ö., Emre, A., Sayar, K., et al. (2009) · PubMed · Cited by 8
Is cardiac output the key to vasovagal syncope? A reevaluation of putative pathophysiology
Raj, S. R. (2008) · Heart Rhythm · doi:10.1016/j.hrthm.2008.09.022 · Cited by 8
“(7) have reported that transcapillary filtration of plasma continues slowly over time with upright tilt.”
BackgroundEvaluating Group Support Systems: Improving Brainstorming Research Methodology
Shaw, D., Eden, C., & Ackermann, F. (2002) · Cited by 8
Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism
Younès, N., St‐Jean, M., Desrochers, M.-J., Thérasse, É., Latour, M., Bourdeau, I., & Lacroix, A. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae155 · Cited by 7
“An increase in epinephrine, norepinephrine, PRA, aldosterone, and vasopressin is seen [60].”
BackgroundSkoog, J., Zachrisson, H., Länne, T., & Lindenberger, M. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00166.2016 · Cited by 7
“Although P-NE is a useful marker of average sympathetic response (15), it provides only an indirect estimate of sympathetic nerve activity (9), and the levels of P-NE during orthostatic stress are mediated by reductions in NE clearance and increases in NE spillover into plasma (18, 28).”
BackgroundManagement of neurogenic orthostatic hypotension in the heart failure patient
Dixon, D., & Muldowney, J. A. S. (2020) · Autonomic Neuroscience · doi:10.1016/j.autneu.2020.102691 · Cited by 7
Tajdini, M., Aminorroaya, A., Tavolinejad, H., Tofighi, S., Jalali, A., Sadeghian, S., Vasheghani‐Farahani, A., Yadangi, S., Shahmansouri, N., Akhondzadeh, S., et al. (2021) · IJC Heart & Vasculature · doi:10.1016/j.ijcha.2021.100789 · Cited by 7
“Activation of the SNS causes increased systemic vascular resistance and heart rate, which results in the maintenance of blood pressure and also blood flow to the brain [21].”
BackgroundDoes sympathetic dysfunction occur before denervation in pure autonomic failure?
Guo, L., Esler, M., Sari, C. I., Phillips, S. E., Lambert, É., Straznicky, N. E., Lambert, G. W., & Corcoran, S. J. (2017) · Clinical Science · doi:10.1042/cs20170240 · Cited by 7
Enhancing Hemodialysis Efficacy through Neuromuscular Stimulation
Madhavan, G., Nemcek, M. A., Martinez, D. G., & McLeod, K. J. (2009) · Blood Purification · doi:10.1159/000167010 · Cited by 6
The Importance of Recognizing Postural Pseudoanemia
Goldner, F., Jacob, G., Raj, S. R., & Robertson, D. (2006) · Comprehensive Therapy · doi:10.1385/comp:32:1:51 · Cited by 6
Self-citationZreik, F., Meshulam, R., Shichel, I., Webb, M., Shibolet, O., & Jacob, G. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00142.2021 · Cited by 5
Self-citation"To drink or not to drink" – is this really the question?
Jacob, G., & Brenner, B. (2008) · Thrombosis and Haemostasis · doi:10.1160/th08-04-0229 · Cited by 5
“Similar results are obtained from sequential measurements of total plasma protein (10, 11), and are supported by direct plasma volume measurement (11).”
BackgroundResultSelf-citationRaj, S. R. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-386525-0.00079-2 · Cited by 4
Raj, S. R., & Sheldon, R. S. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0285-9.00073-9 · Cited by 4
Pappano, A. J., & Wier, W. G. (2013) · Elsevier eBooks · doi:10.1016/b978-0-323-08697-4.00010-1 · Cited by 4
Modeling and simulating human cardiovascular response to acceleration
Zamanian, S. A. (2007) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 4
Metadata
- Authors
- Jacob, G., Ertl, A. C., Shannon, J. R., Furlan, R., Robertson, R. M., & Robertson, D.
- Affiliations
- Vanderbilt University (US)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1998-03-01
- Volume
- 84
- Issue
- 3
- Pages
- 914-921
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2157236879
- Cited by
- 134
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 3 · 2012: 5
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ns033460-03)
- National Heart, Lung, and Blood Institute (P01HL056693, P01 HL-56693)
- National Institute of Neurological Disorders and Stroke (NS 33460)
- National Center for Research Resources (RR00095)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- standing posture, upright posture, plasma volume, neurohumoral response, norepinephrine spillover, epinephrine, vasopressin, plasma renin activity, aldosterone, hemoconcentration, blood pressure, heart rate, sodium excretion, potassium excretion, urine osmolality, plasma osmolarity, renal response
- MeSH terms
- Adult, Aldosterone, Arginine Vasopressin, Blood Pressure, Blood Volume, Catecholamines, Diet, Female, Heart Rate, Humans, Kidney, Male, Middle Aged, Plasma Volume, Posture, Reference Values, Renin, Supine Position, Neurotransmitter Agents
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