Abstract
Chemosensitive Cardiac Afferent Reflexes in Mice: Are they Altered in Hypertrophic Cardiomyopathy?
The FASEB journal, Vol.32(S1), pp.591.4-591.4
04/2018
DOI: 10.1096/fasebj.2018.32.1_supplement.591.4
Abstract
Hypertrophic cardiomyopathy (HCM) is a life‐threatening disease caused by sarcomere gene mutations. Hallmark features include myocyte disarray, left ventricular hypertrophy, fibrosis, and increased risk of arrhythmias and sudden death. Cardiac norepinephrine spillover is augmented in humans with HCM. Similarly, our group has previously reported that cardiac sympathetic tone is increased and vasomotor sympathetic tone is decreased in transgenic mice with cardiac‐specific expression of mutated alpha‐tropomyosin (Glu180Gly), a model of human HCM. Specific aims of this study were to develop protocols to evaluate cardiac reflexes evoked by activation of vagal and ‘sympathetic’ afferents in anesthetized mice, and test the hypothesis that alpha‐tropomyosin mutant HCM mice exhibit enhanced heart rate responses to activation of cardiac ‘sympathetic’ afferents. Cardiac reflexes were evoked via injection of the TRPV1 receptor agonist capsaicin (25 & 50 ng/g, IV) in mice anesthetized with ketamine (91μg/g) and xylazine (9.1 μg/g). Injection of capsaicin (50 ng/g, IV) in C57BL6 mice evoked rapid decreases in heart rate (HR) (−131±17bpm) and mean arterial pressure (MAP) (−30.1±2.7 mmHg) followed by delayed increases in HR (+12.5±7.6bpm) and MAP (+12.7±3.7 mmHg) (n=6, p<0.05). Responses were dose‐dependent and repeatable. Bilateral cervical vagotomy abolished the bradycardic/depressor responses to capsaicin and enhanced the delayed increases in HR (+22.6±4.1bpm) and MAP (+27.6±1.7 mmHg) (n=5). All responses to capsaicin were essentially abolished after ganglionic blockade (p<0.05, n=3) confirming the responses were neurally mediated. The tachycardic response to capsaicin (25ng/g, IV) after vagotomy was significantly (p<0.05) augmented in HCM mice (+32±11bpm, n=5) compared with their wild‐type (WT) controls (+11±3bpm, n=6). In contrast, the MAP response to capsaicin was similar between HCM (+8.5±2.5 mmHg, n=5) and WT (+6.3±1.6 mmHg, n=6). We conclude: (1) Measurements of reflex responses to capsaicin before and after vagotomy enable assessment of both inhibitory and excitatory reflexes in mice, and (2) HCM mice demonstrate an exaggerated tachycardic response to injection of capsaicin, presumably reflecting an increased sensitivity of cardiac ‘sympathetic’ afferent nerves.
Support or Funding Information
NIH T32HL007121, AAS‐Lundbeck Fellowship, NIH HL14388, VA 1BX001414
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Details
- Title: Subtitle
- Chemosensitive Cardiac Afferent Reflexes in Mice: Are they Altered in Hypertrophic Cardiomyopathy?
- Creators
- Robert A. Larson - University of IowaMark W. Chapleau - Veterans Health Administration
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.32(S1), pp.591.4-591.4
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.2018.32.1_supplement.591.4
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- AAS‐Lundbeck Fellowship NIH (HL14388) NIH (T32HL007121) VA (1BX001414)
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984302187802771
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