title: Differential effects of enalapril and losartan on body composition and indices of muscle quality in aged male Fischer 344 × Brown Norway rats.
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.
authors.affiliation: Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL 32610, USA. ccarter@aging.ufl.edu
authors.forename: Christy S
authors.initials: CS
authors.lastname: Carter
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovannini
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovaninni
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Seo
authors.forename: Jameson
authors.initials: J
authors.lastname: DuPree
authors.forename: Drake
authors.initials: D
authors.lastname: Morgan
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Hazel
authors.initials: H
authors.lastname: Lees
authors.forename: Michael
authors.initials: M
authors.lastname: Daniels
authors.forename: Gene B
authors.initials: GB
authors.lastname: Hubbard
authors.forename: Shuko
authors.initials: S
authors.lastname: Lee
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Foster
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Buford
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marzetti
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000375:Aging / Q000473:pathology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000187:drug effects*; D001831:Body Temperature; D001835:Body Weight; D004435:Eating; D004656:Enalapril / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D019808:Losartan / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism; D009043:Motor Activity; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000473:pathology* / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007328:Insulin; D004656:Enalapril; D019808:Losartan