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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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 approximately 400-500 pg/ml.
“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 healthy subjects, the supine plasma norepinephrine level is approximately 200 pg/ml, and upon standing, it doubles before it plateaus after 7.5 min.
“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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BackgroundNeurally Mediated Syncope: Pathophysiology and Implications for Treatment
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“This increase in NE is released from the sympathetic nerve endings by activation of presynaptic β2ARs [24, 25].”
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“55 nmol/L (600 pg/mL), a threshold met by only 2 of the 8 patients in Streeten’s study [8].”
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BackgroundMeasurement of plasma volume using fluorescent silica-based nanoparticles
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“Some studies have shown that non-neurogenic OH was related to autonomic nervous dysfunction and decreased vascular capacity regulation (7).”
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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…”
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“(7) have reported that transcapillary filtration of plasma continues slowly over time with upright tilt.”
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“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).”
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“Similar results are obtained from sequential measurements of total plasma protein (10, 11), and are supported by direct plasma volume measurement (11).”
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- 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 › Surgery › 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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