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Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats

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An Erratum to this article was published on 06 April 2011

Abstract

The primary purpose of the present set of studies was to provide a direct comparison of the effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin receptor blocker losartan on body composition, physical performance, and muscle quality when administered late in life to aged rats. Overall, enalapril treatment consistently attenuated age-related increases in adiposity relative to both placebo and losartan. The maximal effect was achieved after 3 months of treatment (between 24 and 27 months of age), at a dose of 40 mg/kg and was observed in the absence of any changes in physical activity, body temperature, or food intake. In addition, the reduction in fat mass was not due to changes in pathology given that enalapril attenuated age-related increases in tumor development relative to placebo- and losartan-treated animals. Both enalapril and losartan attenuated age-related decreases in grip strength, suggesting that changes in body composition appear dissociated from improvements in physical function and may reflect a differential impact of enalapril and losartan on muscle quality. To link changes in adiposity to improvements in skeletal muscle quality, we performed gene array analyses to generate hypotheses regarding cell signaling pathways altered with enalapril treatment. Based on these results, our primary follow-up pathway was mitochondria-mediated apoptosis of myocytes. Relative to losartan- and placebo-treated rats, only enalapril decreased DNA fragmentation and caspase-dependent apoptotic signaling. These data suggest that attenuation of the severity of skeletal muscle apoptosis promoted by enalapril may represent a distinct mechanism through which this compound improves muscle strength/quality.

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Acknowledgments

This study was supported by the National Institute on Aging Grant AG24526, the University of Florida Institute on Aging, The Claude D. Pepper Older Americans Independence Center Grant NIH P30 AG028740, and the McKnight Foundation.

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Authors and Affiliations

  1. Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, 32610, USA

    Christy S. Carter, Silvia Giovaninni, Dong-Oh Seo, Jameson DuPree, Hazel Lees, Thomas W. Buford & Emanuele Marzetti

  2. Department of Gerontology, Geriatrics and Physical Sciences, Catholic University of the Sacred Heart, Rome, Italy

    Silvia Giovaninni

  3. Department of Psychiatry, University of Florida, Gainesville, FL, 32610, USA

    Drake Morgan

  4. Department of Pharmacy, Longevity Science and Technology Institutes, Research Institute for Drug Development, Pusan National University, Geumjeong-gu, Busan, 609-735, South Korea

    Hae Young Chung

  5. Department of Statistics, University of Florida, Gainesville, FL, 32610, USA

    Michael Daniels

  6. Barshop Institute and Department of Pathology, University of Texas Health Science Center, San Antonio, TX, 78245, USA

    Gene B. Hubbard & Yuji Ikeno

  7. Audie Murphy VA Hospital (STVHCS), San Antonio, TX, 78245, USA

    Shuko Lee & Yuji Ikeno

  8. Department of Neuroscience, University of Florida, Gainesville, FL, 32610, USA

    Thomas C. Foster

  9. Department of Orthopedics and Traumatology, Catholic University of the Sacred Heart, Rome, Italy

    Emanuele Marzetti

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  1. Christy S. Carter
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  7. Hazel Lees
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  9. Gene B. Hubbard
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  10. Shuko Lee
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  11. Yuji Ikeno
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  12. Thomas C. Foster
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  13. Thomas W. Buford
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  14. Emanuele Marzetti
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Correspondence to Christy S. Carter.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11357-011-9243-3

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Carter, C.S., Giovaninni, S., Seo, DO. et al. Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats. AGE 33, 167–183 (2011). https://doi.org/10.1007/s11357-010-9196-y

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  • DOI: https://doi.org/10.1007/s11357-010-9196-y

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