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Cited by 59Cardiovascular Syncope and Autonomic DisordersRenin-Angiotensin System StudiesHeart Rate Variability and Autonomic Control

Defects in cutaneous angiotensin-converting enzyme 2 and angiotensin-(1-7) production in postural tachycardia syndrome

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Stewart, Julian M., Ocon, Anthony J., Clarke, Debbie, Taneja, Indu, Medow, Marvin S.·2009·Hypertension
DOI 10.1161/hypertensionaha.108.127357PMC PMC2765216
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Abstract

Postural tachycardia syndrome (POTS) is associated with increased plasma angiotensin II (Ang II). Ang II administered in the presence of NO synthase inhibition with nitro-l-arginine (NLA) and Ang II type 1 receptor blockade with losartan produces vasodilation during local heating in controls. We tested whether this angiotensin-mediated vasodilation occurs in POTS and whether it is related to angiotensin-converting enzyme 2 (ACE2) and Ang-(1-7). We used local cutaneous heating to 42°C and laser Doppler Flowmetry to assess NO-dependent conductance at 4 calf sites in 12 low-flow POTS and in 12 control subjects 17.6 to 25.5 years of age. We perfused Ringer’s solution through intradermal microdialysis catheters and performed local heating. We perfused one catheter with NLA (10 mmol/L)+losartan (2 μg/L) and repeated heating, and NLA+losartan+Ang II (10 μmol/L), repeating heating a third time. A second catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+DX600 (1 mmol/L; a selective ACE2 inhibitor), and reheated. A third catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+Ang-(1-7) (100 μmol/L), and reheated. The fourth catheter received Ang-(1-7) then reheated a second time only. Angiotensin-mediated vasodilation was present in control but not POTS. Ang-mediated dilation was eliminated by DX600, indicating an ACE2-related effect. Ang-mediated vasodilation was restored in POTS by Ang-(1-7). When administered alone during locally mediated heating, Ang-(1-7) improved the NO-dependent local heating response. ACE2 effects are blunted in low-flow POTS and restored by the ACE2 product Ang-(1-7). Data imply impaired catabolism of Ang II through the ACE2 pathway. Vasoconstriction in POTS may result from a reduction in Ang-(1-7) and an increase in Ang II.

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Crossref · 10.1161/hypertensionaha.108.127357

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49 of 49 references verified0 citation errors · 0 not checkable

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  • Some POTS patients have persistently low plasma volumes, which evidence suggests is perhaps secondary to impaired function of the renin-angiotensin-aldosterone system.

    “Some POTS patients have been noted to have persistently low plasma volumes (32,(42)(43)(44), which evidence suggests is perhaps secondary to impaired function of the renin-angiotensin-aldosterone system.”

    From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [42]

    The Introduction (page unavailable) describes a low-flow POTS subgroup with hypovolemia. The Discussion (page unavailable) suggests an ACE2-related angiotensin defect, but links it to excessive vasoconstriction, not to the cause of low plasma volume. The paper also does not establish that the low volume is persistent. (LLM, conf=0.84)

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  • Others have elevated plasma angiotensin II levels suggesting inadequate angiotensin-converting enzyme 2 activity.

    “Others have elevated plasma angiotensin II levels suggesting inadequate angiotensin-converting enzyme 2 activity (42,44).”

    From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [42]

  • Some POTS patients have inappropriately low plasma renin activity and aldosterone levels resulting in inadequate renal sodium retention.

    “Some have inappropriately low plasma renin activity and aldosterone levels resulting in inadequate renal sodium retention (42,44).”

    From Postural Orthostatic Tachycardia Syndrome (2019) · cites this paper as [42]

    The Introduction describes hypovolemia in a low-flow POTS subgroup and says increased angiotensin II was not accounted for by changes in renin. Neither it nor the other passages found by searching for renin, aldosterone, and sodium retention addresses inappropriately low plasma renin activity and aldosterone causing inadequate renal sodium retention. Page numbers were not available in our copy. (LLM, conf=0.76)

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2 of the 51 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. [16]Harrison DG Cai H Landmesser U Griendling KK Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease J Renin Angiotensin Aldosterone Syst 2003 4 51 61 12806586
  2. [24]Santos RA Ferreira AJ Simoes E Silva AC Recent advances in the ACE2-Ang-(1–7)-Mas axis Exp Physiol 2008 93 519 527 18310257

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Authors
Stewart, J. M., Ocon, A. J., Clarke, D., Taneja, I., & Medow, M. S.
Affiliations
New York Medical College (US)
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2009-05
Volume
53
Issue
5
Pages
767-774
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hypertensionaha.108.127357
PMC
PMC2765216
OpenAlex
W2111069517
Cited by
59
References
51
Citations by year
2025: 1 · 2024: 3 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 7 · 2013: 3 · 2012: 7
FWCI
5.40
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL087803, R01HL074873, R21HL091948)
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, angiotensin-converting enzyme 2, angiotensin-(1-7), angiotensin II, nitric oxide, vasodilation, nitro-L-arginine, losartan, ACE2 inhibition, vasoconstriction, microcirculation
MeSH terms
Angiotensin-Converting Enzyme 2, Adolescent, Adult, Angiotensin I, Female, Humans, Peptidyl-Dipeptidase A, Male, Peptide Fragments, Skin, Vasodilation, Nitroarginine, Losartan, Postural Orthostatic Tachycardia Syndrome

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