Journal article
Differential Engagement of Inhibitory and Excitatory Cardiopulmonary Reflexes by Capsaicin and Phenylbiguanide in C57BL/6 Mice
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.324(3), pp.R336-R344
02/14/2023
DOI: 10.1152/ajpregu.00102.2022
PMCID: PMC9942883
PMID: 36622083
Abstract
The Bezold-Jarisch reflex is a powerful inhibitory reflex initiated by activation of cardiopulmonary vagal nerves during myocardial ischemia, hemorrhage, and orthostatic stress leading to bradycardia, vasodilation, hypotension and vasovagal syncope. This clinically relevant reflex has been studied by measuring heart rate (HR) and mean arterial pressure (MAP) responses to injections of a variety of chemical compounds. We hypothesized that reflex responses to different compounds vary due to differential activation of vagal afferent subtypes and/or variable co-activation of excitatory afferents. HR and MAP responses to intravenous injections of the TRPV1 agonist capsaicin and the serotonin 5-HT 3 receptor agonist phenylbiguanide (PBG) were measured in anesthetized C57BL/6 mice before and after bilateral cervical vagotomy. Capsaicin and PBG evoked rapid dose-dependent decreases in HR and MAP followed by increases in HR and MAP above baseline. Bezold-Jarisch reflex responses were abolished after vagotomy, while the delayed tachycardic and pressor responses to capsaicin and PBG were differentially enhanced. The relative magnitude of bradycardic vs. depressor responses (↓HR/↓MAP) in vagus-intact mice was greater with capsaicin. In contrast, after vagotomy the magnitude of excitatory tachycardic vs. pressor responses (↑HR/↑MAP) was greater with PBG. While capsaicin-induced increases in MAP and HR post-vagotomy were strongly attenuated or abolished after administration of the ganglionic blocker hexamethonium, PBG-induced increases in MAP and HR were mildly attenuated and unchanged, respectively. We conclude that responses to capsaicin and PBG differ in mice, with implications for delineating the role of endogenous agonists of TRPV1 and 5-HT 3 receptors in evoking cardiopulmonary reflexes in pathophysiological states.
Details
- Title: Subtitle
- Differential Engagement of Inhibitory and Excitatory Cardiopulmonary Reflexes by Capsaicin and Phenylbiguanide in C57BL/6 Mice
- Creators
- Robert A. Larson - University of IowaMark W. Chapleau - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.324(3), pp.R336-R344
- DOI
- 10.1152/ajpregu.00102.2022
- PMID
- 36622083
- PMCID
- PMC9942883
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Grant note
- name: American Autonomic Society, award: Lundbeck Fellowship; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: P01HL14388; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: F32HL140880
- Language
- English
- Electronic publication date
- 01/09/2023
- Date published
- 02/14/2023
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984358158002771
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