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

Christy S. Carter, Silvia Giovaninni, Dong Oh Seo, Jameson Dupree, Drake Morgan, Hae Young Chung, Hazel Lees, Michael Daniels, Gene B. Hubbard, Shuko Lee, Yuji Ikeno, Thomas C. Foster, Thomas W. Buford, Emanuele Marzetti

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)167-183
Number of pages17
JournalAge
Volume33
Issue number2
DOIs
StatePublished - Jun 2011

Fingerprint

Enalapril
Losartan
Body Composition
Muscles
Placebos
Adiposity
Skeletal Muscle
Apoptosis
Angiotensin Receptor Antagonists
Muscle Strength
Hand Strength
DNA Fragmentation
Caspases
Body Temperature
Angiotensin-Converting Enzyme Inhibitors
Muscle Cells
Mitochondria
Therapeutics
Eating
Fats

Keywords

  • Age-related adiposity
  • Body composition
  • Muscle quality
  • Physical function
  • Renin-angiotensin system
  • Sarcopenia

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Carter, C. S., Giovaninni, S., Seo, D. O., Dupree, J., Morgan, D., Chung, H. Y., ... Marzetti, E. (2011). Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 x Brown Norway rats. Age, 33(2), 167-183. https://doi.org/10.1007/s11357-010-9196-y

Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 x Brown Norway rats. / Carter, Christy S.; Giovaninni, Silvia; Seo, Dong Oh; Dupree, Jameson; Morgan, Drake; Chung, Hae Young; Lees, Hazel; Daniels, Michael; Hubbard, Gene B.; Lee, Shuko; Ikeno, Yuji; Foster, Thomas C.; Buford, Thomas W.; Marzetti, Emanuele.

In: Age, Vol. 33, No. 2, 06.2011, p. 167-183.

Research output: Contribution to journalArticle

Carter, CS, Giovaninni, S, Seo, DO, Dupree, J, Morgan, D, Chung, HY, Lees, H, Daniels, M, Hubbard, GB, Lee, S, Ikeno, Y, Foster, TC, Buford, TW & Marzetti, E 2011, 'Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 x Brown Norway rats', Age, vol. 33, no. 2, pp. 167-183. https://doi.org/10.1007/s11357-010-9196-y
Carter, Christy S. ; Giovaninni, Silvia ; Seo, Dong Oh ; Dupree, Jameson ; Morgan, Drake ; Chung, Hae Young ; Lees, Hazel ; Daniels, Michael ; Hubbard, Gene B. ; Lee, Shuko ; Ikeno, Yuji ; Foster, Thomas C. ; Buford, Thomas W. ; Marzetti, Emanuele. / Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 x Brown Norway rats. In: Age. 2011 ; Vol. 33, No. 2. pp. 167-183.
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