Acute and Persistent Cardiovascular Effects of Menthol E‐Cigarettes in Mice

Although e-cigarettes provide an alternative to conventional smoking, the cardiovascular impacts of e-cigarette use are unresolved. The popularity of menthol e-cigarettes has surged recently and may escalate further with bans on combustible menthol cigarettes and e-cigarette flavors other than menth...

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Published in:Journal of the American Heart Association Vol. 14; no. 9; p. e037420
Main Authors: Ramalingam, Anand R., Kucera, Cory, Srivastava, Shweta, Paily, Romith, Stephens, Dawson, Lorkiewicz, Pawel, Wilkey, Daniel W., Merchant, Michael, Bhatnagar, Aruni, Carll, Alex P.
Format: Journal Article
Language:English
Published: England John Wiley and Sons Inc 06.05.2025
Wiley
Subjects:
Aerosols
Animals
arrhythmia
Arrhythmias, Cardiac - chemically induced
Arrhythmias, Cardiac - metabolism
Arrhythmias, Cardiac - physiopathology
atenolol
blood pressure
Blood Pressure - drug effects
bradycardia
Disease Models, Animal
E-Cigarette Vapor
Electrocardiography
Electronic Nicotine Delivery Systems
Epinephrine - urine
flavor
Flavoring Agents
Heart Rate - drug effects
Male
Menthol - administration & dosage
Menthol - adverse effects
Menthol - toxicity
Mice
Mice, Inbred C57BL
Nicotine
Original Research
Time Factors
Vaping - adverse effects
flavor
blood pressure
bradycardia
arrhythmia
atenolol
ISSN:2047-9980, 2047-9980
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Summary:Although e-cigarettes provide an alternative to conventional smoking, the cardiovascular impacts of e-cigarette use are unresolved. The popularity of menthol e-cigarettes has surged recently and may escalate further with bans on combustible menthol cigarettes and e-cigarette flavors other than menthol and tobacco. Despite recent evidence in mice that menthol e-cigarettes acutely induce cardiac arrhythmias, the impacts of repeated menthol e-cigarette use on cardiovascular function and the cardiac proteome remain unclear. We therefore investigated the acute and persistent cardiovascular effects of menthol e-cigarettes in a mouse model. Adult C57BL/6J mice with ECG and blood pressure radiotransmitters were exposed to e-cigarette aerosols (180-270 puffs/day; n=4-8/group). One-day exposures to nicotine-containing e-cigarette aerosols depressed heart rate variability regardless of flavor, but menthol e-cigarette aerosols uniquely increased heart rate and urine epinephrine and elicited spontaneous ventricular premature beats. Menthol e-cigarette aerosols consistently increased blood pressure acutely, and this effect recurred throughout the 20-day regimen. Pretreatment with atenolol abolished e-cigarette-induced arrhythmias, suggesting the involvement of β1-adrenoceptors. After 4 weeks of exposure to JUUL Menthol aerosol, mice had basal sinus bradycardia that persisted up to 3 weeks after exposure cessation. After cessation, e-cigarette-exposed mice also exhibited an altered chronotropic response to restraint stress and prolonged ventricular repolarization (corrected QT interval). Integrated proteomic and phosphoproteomic analysis of cardiac tissue harvested from mice exposed to menthol e-cigarette aerosols for 5 and 20 days revealed molecular signatures of dilated and arrhythmogenic cardiomyopathy. Exposure to menthol e-cigarette aerosols induces persistent cardiovascular autonomic imbalance in vivo. These findings raise the possibility of similar effects in humans using mentholated e-cigarettes.
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For Sources of Funding and Disclosures, see page 15.
This manuscript was sent to Barry London, MD, PhD, Senior Guest Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.124.037420
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.124.037420