Abstract
Differential sympathetic activation and blunted cardiovascular diurnal rhythms in a mouse model of hypertrophic cardiomyopathy
The FASEB journal, Vol.24(S1), pp.809.17-809.17
04/2010
DOI: 10.1096/fasebj.24.1_supplement.809.17
Abstract
Mutations in the sarcomeric protein α‐tropomyosin (αTM) cause hypertrophic cardiomyopathy (HCM) in humans and mice. We recently reported that mice with HCM, induced by cardiac‐targeted transgenic expression of mutated αTM (Glu180Gly), exhibit myocyte disarray, cardiac fibrosis, left ventricular (LV) dysfunction, and decreased baroreflex sensitivity [Hypertension 2009]. In this study, we tested the hypothesis that sympathetic activity is increased and diurnal variations in heart rate (HR) and blood pressure (BP) are blunted in HCM mice. Cardiac function, BP, HR, locomotor activity and electrocardiograms were measured by echocardiography and telemetry, respectively, in 12–15wk old wild‐type (WT) and HCM mice (n=4, per group). LV ejection fraction and mean BP were significantly reduced in HCM mice. Diurnal changes (night‐day) in BP and HR were markedly attenuated in HCM, despite preserved diurnal changes in locomotor activity (Table). Interestingly, cardiac sympathetic tone (HR response to β‐blocker propranolol) was markedly increased in HCM mice, while vasomotor sympathetic tone (BP response to ganglionic blocker chlorisondamine) was reduced (Table). Furthermore, extensive thrombus in enlarged atria and cardiac arrhythmias were observed in HCM mice.
*P<0.05, HCM vs. WT mice
WT
HCM
Diurnal BP (ΔmmHg)
23±3
10±2 *
Diurnal HR (Δbpm)
76±11
30±14 *
Diurnal Activity (Δcounts/min)
3.9±0.9
6.3±0.8
Cardiac Sympathetic Tone (Δbpm )
−109±12
−200±9 *
Vasomotor Sympathetic Tone (ΔmmHg)
−60±2
−31±4 *
We conclude that cardiovascular diurnal rhythms are blunted and cardiac sympathetic activity is increased in HCM mice. We speculate that altered activity of cardiac afferents innervating the pathologic heart may trigger decreased vasomotor and increased cardiac sympathetic tone and arrhythmias in HCM.
Details
- Title: Subtitle
- Differential sympathetic activation and blunted cardiovascular diurnal rhythms in a mouse model of hypertrophic cardiomyopathy
- Creators
- Rasna Sabharwal - University of IowaRobert M. Weiss - University of IowaKathy Zimmerman - Vet Aff Med CtrMark W. Chapleau - Vet Aff Med Ctr
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.24(S1), pp.809.17-809.17
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.24.1_supplement.809.17
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2010
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984302999902771
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