Clinical and Physiological Effects of an Acute α-1 Adrenergic Agonist and a β-1 Adrenergic Antagonist in Chronic Orthostatic Intolerance
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Background— Adrenergic agents are commonly used in the treatment of chronic orthostatic intolerance with postural tachycardia syndrome (POTS). POTS may be associated with increased limb blood flow (“high flow”) and defective orthostatic vasoconstriction or decreased limb blood flow (“low flow”) and potentially with small blood volume. Methods and Results— We investigated the consequences of short-term intravenous administration of an α-1 adrenergic agonist, phenylephrine, and a β-1 adrenergic antagonist, esmolol, in 14 patients with POTS aged 13 to 19 years. Indices of heart rate and blood pressure variability, peripheral blood flow, and arterial resistance were assessed, and the capacitance relation was computed for every subject using venous occlusion plethysmography. Patients were tilted to 35° upright while medicated and while unmedicated, and measurements were repeated. Phenylephrine improved orthostatic tolerance and normalized hemodynamics and indices of heart rate/blood pressure variability while supine and while upright, producing significant peripheral vasoconstriction and venoconstriction (20% capacitance change). Esmolol did not improve orthostatic tolerance or hemodynamics. A subgroup of low-flow POTS patients had exaggerated venoconstriction to phenylephrine (50% capacitance change) but others had no response. Conclusions— Phenylephrine, but not esmolol, improves orthostatic tolerance and hemodynamics in POTS. This lends support to the use of oral α-1 agonists in the treatment of patients with chronic orthostatic intolerance.
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Animal or experimental models of orthostatic intolerance showed no improvement in orthostatic tolerance with propranolol or esmolol.
“Unfortunately, in experimental models of orthostatic intolerance, neither propranolol 15, 16 nor esmolol 17 were found to improve orthostatic tolerance.”
From Propranolol Decreases Tachycardia and Improves Symptoms in the Postural Tachycardia Syndrome: Less Is More (2009) · cites this paper as [17]
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- Authors
- Stewart, J. M., Munoz, J., & Weldon, A.
- Affiliations
- New York Medical College (US)
- ORCID
- Stewart, Julian M.
- Venue
- Circulation
- Published
- 2002-12-03
- Volume
- 106
- Issue
- 23
- Pages
- 2946-2954
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2112148148
- Cited by
- 71
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 7
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL066007, 5R01HL66007)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- postural orthostatic tachycardia syndrome, orthostatic intolerance, phenylephrine, esmolol, alpha-1 adrenergic agonists, peripheral blood flow, venoconstriction, heart rate variability, blood pressure variability, venous capacitance
- MeSH terms
- Adolescent, Adrenergic alpha-Agonists, Adrenergic beta-Antagonists, Adult, Blood Pressure, Chronic Disease, Electrocardiography, Female, Forearm, Humans, Hypotension, Orthostatic, Infusions, Intravenous, Leg, Male, Phenylephrine, Posture, Propanolamines, Regional Blood Flow, Syndrome, Tachycardia, Treatment Outcome, Tilt-Table Test, Adrenergic alpha-1 Receptor Agonists, Adrenergic beta-1 Receptor Antagonists
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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