Abnormalities of angiotensin regulation in postural tachycardia syndrome
Open accessAbstract
Background Postural tachycardia syndrome (POTS) is a disorder characterized by excessive orthostatic tachycardia and significant functional disability. We previously reported that POTS patients have low blood volume and inappropriately low plasma renin activity (PRA) and aldosterone. In this study, we sought to more fully characterize the renin-angiotensin-aldosterone system (RAAS) to gain a better understanding of the pathophysiology of POTS. Objective The purpose of this study was to prospectively assess the plasma levels of angiotensin (Ang) peptides and their relationship to other RAAS components in patients with POTS compared with healthy controls. Methods Heart rate, PRA, Ang I, Ang II, Ang (1-7), and aldosterone were measured in POTS patients (n = 38) and healthy controls (n = 13) while they were consuming a sodium-controlled diet. Results POTS patients had larger orthostatic increases in heart rate than did controls (52 ± 3 [mean ± SEM] bpm vs 27 ± 6 bpm, P = .001). Plasma Ang II was significantly higher in POTS patients (43 ± 3 pg/mL vs 28 ± 3 pg/mL, P = .006), whereas plasma Ang I and angiotensin 1-7 [Ang-(1-7)] were similar between groups. Despite the twofold increase of Ang II, POTS patients trended to lower PRA levels than did controls (0.9 ± 0.1 ng/mL/h vs 1.6 ± 0.5 ng/mL/h, P = .268) and lower aldosterone levels (4.6 ± 0.8 pg/mL vs 10.0 ± 3.0 pg/mL, P = .111). Estimated angiotensin-converting enzyme-2 (ACE2) activity was significantly lower in POTS patients tha…
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POTS patients have impaired ability of the renin-angiotensin aldosterone system to expand blood volume.
“While circulating angiotensin II levels are high, POTS patients have impaired ability of the RAAS to expand blood volume (Li et al., 2015a; Mustafa et al., 2011; Raj et al., 2005; Stewart et al., 2006b).”
From Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1 (2021) · cites this paper as Mustafa et al., 2011
Circulating angiotensin II levels are reported elevated in POTS without a parallel increase in its metabolite angiotensin (1-7).
“Circulating angiotensin II levels have been reported to be elevated but without a parallel increase in its metabolite angiotensin (1-7) [50;51].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [50]
These paradoxical findings suggest that POTS patients might have decreased angiotensin II metabolism and that dysregulation by the renin-angiotensin-aldosterone system might contribute to hypovolemia in POTS.
“These paradoxical findings suggest that POTS patients might have decreased angiotensin II metabolism and that dysregulation by the renin-angiotensin-aldosterone system might contribute to hypovolemia in POTS [50;51].”
From Postural tachycardia syndrome: beyond orthostatic intolerance (2015) · cites this paper as [50]
Plasma angiotensin 2 levels in some POTS patients are elevated on the order of 2-3 times higher than healthy controls.
“Further investigations into the renin-angiotensin aldosterone system (RAAS) revealed that plasma angiotensin 2 (Ang-II) levels in some POTS patients are elevated (on the order of 2-3 times higher) when compared to healthy controls (35, 36).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [36]
Hyperadrenergic POTS is an important endophenotype of POTS with the characteristic neurohormonal hallmark of elevated upright plasma norepinephrine.
“Hyperadrenergic POTS is an important endophenotype of POTS with the characteristic, neurohormonal hallmark of elevated upright plasma norepinephrine (34, 36).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [36]
Levels of plasma epinephrine appear to be similar between POTS patients and healthy subjects.
“Levels of plasma epinephrine appear to be similar between POTS patients and healthy subjects (34, 36).”
From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [36]
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 [36]
Many POTS patients have decreased plasma volume.
“Many POTS patients have a decreased plasma volume (6–8) and high standing plasma norepinephrine (9).”
From Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome (2021) · cites this paper as [8]
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References 38 · Cited by 62
- Authors
- Mustafa, H. I., Garland, E. M., Biaggioni, I., Black, B. K., Dupont, W. D., Robertson, D., & Raj, S. R.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Raj, Satish R.
- Venue
- Heart Rhythm
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 8
- Issue
- 3
- Pages
- 422-428
- ISSN
- 1547-5271 (ISSN-L)
- PMC
- PMC3050076
- OpenAlex
- W2111329928
- Cited by
- 62
- References
- 38
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Heart Rhythm (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University
- National Heart, Lung, and Blood Institute (R01HL071784, P01HL056693, R01HL102387, P01 HL-56693)
- National Institute of Neurological Disorders and Stroke (R01NS055670)
- National Center for Research Resources (KL2RR024977, TL1RR024978, UL1RR024975, K23RR020783)
- 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 › Heart Rate Variability and Autonomic Control
- Keywords
- postural orthostatic tachycardia syndrome, renin-angiotensin-aldosterone system, angiotensin II, angiotensin I, angiotensin-(1-7), angiotensin-converting enzyme 2, plasma renin activity, aldosterone, orthostatic tachycardia, pathophysiology
- MeSH terms
- Adult, Angiotensin II, Female, Hemodynamics, Humans, Male, Menstrual Cycle, Prospective Studies, Renin-Angiotensin System, Postural Orthostatic Tachycardia Syndrome
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