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Hypovolemia in Syncope and Orthostatic Intolerance Role of the Renin-Angiotensin System
Abstract
Purpose Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed.Methods and materials We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations.Results There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level.Conclusions Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.
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“but cautioned that a high plasma norepinephrine could be due not only to a primary hyperadrenergic state but could also reflect a compensatory sympathetic activation secondary to a partial neuropathy,9 a concern shared by others.24”
From Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine (2024) · cites this paper as [9]
In the citing paper
“Studies that reported a plasma volume deficit in POTS patients despite a normal- to high-sodium diet (≥150 mEq sodium/day) (6, 14, 15), suggest that patients may not effectively respond to dietary sodium with plasma volume expansion.”
From Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome (2021) · cites this paper as [14]
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Metadata
- Authors
- Jacob, G., Robertson, D., Mosqueda-Garcia, R., Ertl, A. C., Robertson, R. M., & Biaggioni, I.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Robertson, David
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 103
- Issue
- 2
- Pages
- 128-133
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2123169434
- Cited by
- 164
- References
- 30
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 8 · 2013: 6 · 2012: 5
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl044589-05)
- National Heart, Lung, and Blood Institute (HL-44589)
- 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 › Heart Rate Variability and Autonomic Control
- Keywords
- orthostatic intolerance, syncope, hypovolemia, renin-angiotensin system, plasma renin activity, plasma aldosterone, norepinephrine, orthostatic tachycardia, blood volume, autonomic dysfunction, sympathetic denervation
- MeSH terms
- Adolescent, Adult, Blood Pressure, Blood Volume, Catecholamines, Female, Heart Rate, Humans, Hypotension, Orthostatic, Male, Renin-Angiotensin System, Syncope
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