Antioxidant tempol reverses autonomic dysregulation and neurogenic hypertension in acid-sensing ion channel 2 deficient mice

Rasna Sabharwal; Francois M. Abboud; Mark W. Chapleau

doi:10.1016/j.autneu.2025.103376

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Antioxidant tempol reverses autonomic dysregulation and neurogenic hypertension in acid-sensing ion channel 2 deficient mice

Journal article

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Peer reviewed

Antioxidant tempol reverses autonomic dysregulation and neurogenic hypertension in acid-sensing ion channel 2 deficient mice

Rasna Sabharwal, Francois M. Abboud and Mark W. Chapleau

Autonomic neuroscience, Vol.263, 103376

02/01/2026

DOI: 10.1016/j.autneu.2025.103376

PMCID: PMC12790828

PMID: 41456535

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Abstract

Acid-Sensing Ion Channel 2 (ASIC2) has been implicated in mechanosensation. We reported previously that ASIC2 is highly expressed in aortic baroreceptor neurons and contributes to baroreceptor mechanotransduction; and that ASIC2 deficient mice exhibit decreased baroreflex sensitivity (BRS), sympathovagal imbalance and neurogenic hypertension. Oxidative stress is widely considered an important contributor to hypertension. The major goal of this study was to determine if treatment of ASIC2 mice with the antioxidant tempol attenuates baroreflex/autonomic dysfunction and hypertension. Blood pressure (BP), heart rate (HR) and locomotor activity were measured by telemetry in conscious, control C57BL/6 and ASIC2 male mice, before and after administration of tempol in drinking water (1 mM) for two weeks. Cardiac sympathetic tone, mean arterial BP and BP variability were higher, and cardiac vagal tone and BRS were lower in ASIC2 mice, compared with controls (P < 0.05). Oxidative stress measured by mRNA expression of NADPH oxidase subunits (Nox2, Nox4, p22phox) and dihydroethidium (DHE) fluorescence was increased significantly (P < 0.05) in ASIC2 mice in a tissue-specific manner (sympathetic and nodose ganglia > > brain stem > > skeletal muscle, with no change in aorta). Treatment with tempol strongly attenuated DHE fluorescence and restored autonomic regulation and BP to control levels in ASIC2 mice, while not affecting these phenotypes in control mice. We conclude: (1) oxidative stress in ASIC2 mice is prominent in the autonomic nervous system but not present in aorta; and (2) the antioxidant tempol reverses decreased BRS, sympathovagal imbalance and hypertension in ASIC2 mice; effects that are associated with decreased oxidative stress.

Oxidative Stress

Acid-sensing ion channels

Baroreceptor reflex

Neurogenic hypertension

Sympathovagal imbalance

Tempol

Details

Title: Subtitle: Antioxidant tempol reverses autonomic dysregulation and neurogenic hypertension in acid-sensing ion channel 2 deficient mice
Creators: Rasna Sabharwal - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, United States
Francois M. Abboud - University of Iowa
Mark W. Chapleau - University of Iowa
Resource Type: Journal article
Publication Details: Autonomic neuroscience, Vol.263, 103376
DOI: 10.1016/j.autneu.2025.103376
PMID: 41456535
PMCID: PMC12790828
NLM abbreviation: Auton Neurosci
ISSN: 1566-0702
eISSN: 1872-7484
Publisher: ELSEVIER
Grant note: 0855944G / American Heart Association (100000968) R01 HL149677 / National Institutes of Health (100000002) R21 AG070188 / National Institutes of Health (100000002) 1BX001414 / U.S. Department of Veterans Affairs (100000738) HL14388 / National Institutes of Health (100000002)
Language: English
Date published: 02/01/2026
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9985113260002771

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