Overexpressed cardiac Gsα in rabbits
Abstract
We overexpressed cardiac Gsalpha in rabbits using the beta-myosin heavy chain promoter. Gsalpha protein levels in the heart were increased 3-fold by Western blotting in both juvenile (3-4 months), adult (8-10 months), and older (11-16 months) rabbits, compared with wild type (WT) littermates. In transgenic (TG) rabbits, baseline levels of heart rate were elevated, P<0.05 (268+/-17 vs. 209+/-15 beats/min), as well as left ventricular (LV) contractility (LV dP/dt 5475+/-482 vs. 3740+/-246 mm Hg/s). These values and LV ejection fraction remained significantly elevated in older TG rabbits (11-16 months). However, maximal levels of LV dP/dt and heart rate with a high dose of isoproterenol (0.4 microg/kg/min) were similar in adult TG and WT rabbits. In isolated myocytes from the LV of adult rabbits, baseline percent contraction was increased, P<0.05, in TG (11.2+/-0.5%) compared to WT (9.3+/-0.5%), while maximal responses to isoproterenol (100 nM) were similar in adult TG (16.2+/-0.5%) and WT myocytes (15.6+/-0.4%). Although TG mice with overexpressed cardiac Gsalpha develop cardiomyopathy at 8-12 months of age, even at 16 months of age, there was no evidence of cardiomyopathy either in terms of LV function or histology in TG rabbits. In addition, Gialpha was elevated in the LV of adult (8-10 months old) TG rabbits compared to WT, but not in juvenile (3-5 months old) TG rabbits. Although both TG mice and rabbits with overexpressed cardiac Gsalpha exhibited enhanced heart rate and contractility, the TG rabbit does not develop cardiomyopathy, potentially due to a compensatory increase in Gialpha.
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Some rabbit models have shown divergent effects of a particular manipulation compared with mouse models.
“Some rabbit models have actually shown divergent effects of a particular manipulation as compared to mouse models (Nishizawa, et al., 2006).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Nishizawa, et al., 2006
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Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484 · see citing works
- Authors
- Nishizawa, T., Vatner, S. F., Hong, C., Shen, Y.-T., Hardt, S. E., Robbins, J., Ishikawa, Y., Sadoshima, J., & Vatner, D. E.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Rutgers New Jersey Medical School (US)
- Corresponding author
- Vatner, Dorothy E.
- ORCID
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 41
- Issue
- 1
- Pages
- 44-50
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W2090559216
- Cited by
- 11
- References
- 20
- Citations by year
- 2022: 1 · 2020: 1 · 2013: 2
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG023137, AG14121, R01AG014121, AG-023137)
- National Heart, Lung, and Blood Institute (HL59139, R01HL067724, HL69020, HL-33107, HL-67724, P01HL059139, P01HL069020)
- National Institute of General Medical Sciences (R01GM067773, GM-67773)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- transgenic rabbits, heart rate, left ventricular contractility, ejection fraction, isoproterenol response, cardiomyopathy, cardiomyocytes
- MeSH terms
- Adenylyl Cyclases, Animals, Animals, Newborn, Female, Heart Failure, Heart Rate, Male, Myocardial Contraction, Cardiomyopathies, Rabbits, Gene Expression Regulation, Developmental, GTP-Binding Protein alpha Subunits, Gs, GTP-Binding Protein alpha Subunits, Gi-Go, Animals, Genetically Modified, Myocytes, Cardiac
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