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[PMID]: | 29180454 |
[Au] Autor: | Engeli S; Stinkens R; Heise T; May M; Goossens GH; Blaak EE; Havekes B; Jax T; Albrecht D; Pal P; Tegtbur U; Haufe S; Langenickel TH; Jordan J |
[Ad] Endereço: | From the Institute of Clinical Pharmacology (S.E., M.M., S.H., J.J.), Institute of Sports Medicine (U.T.), Hannover Medical School, Germany; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism (R.S., G.H.G., E.E.B.), Division of Endocrinology, Department |
[Ti] Título: | Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension. |
[So] Source: | Hypertension;71(1):70-77, 2018 01. | [Is] ISSN: | 1524-4563 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine. This was a multicenter, randomized, double-blind, active-controlled, parallel-group study enrolling subjects with abdominal obesity and moderate hypertension (mean sitting systolic blood pressure ≥130-180 mm Hg). Lipolysis during rest and exercise was assessed by microdialysis and [1,1,2,3,3- H]-glycerol tracer kinetics. Energy expenditure and substrate oxidation were measured simultaneously using indirect calorimetry. Plasma nonesterified fatty acids, glycerol, insulin, glucose, adrenaline and noradrenaline concentrations, blood pressure, and heart rate were also determined. Exercise elevated plasma glycerol, free fatty acids, and interstitial glycerol concentrations and increased the rate of glycerol appearance. However, exercise-induced stimulation of lipolysis was not augmented on sacubitril/valsartan treatment compared with amlodipine treatment. Furthermore, sacubitril/valsartan did not alter energy expenditure and substrate oxidation during exercise compared with amlodipine treatment. In conclusion, sacubitril/valsartan treatment for 8 weeks did not elicit clinically relevant changes in exercise-induced lipolysis or substrate oxidation in obese patients with hypertension, implying that its beneficial cardiovascular effects cannot be explained by changes in lipid metabolism during exercise. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01631864. |
[Mh] Termos MeSH primário: |
Aminobutiratos Anlodipino/administração & dosagem Exercício/fisiologia Hipertensão Neprilisina Obesidade Abdominal Tetrazóis
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[Mh] Termos MeSH secundário: |
Tecido Adiposo/metabolismo Aminobutiratos/administração & dosagem Aminobutiratos/efeitos adversos Aminobutiratos/farmacocinética Antagonistas de Receptores de Angiotensina/administração & dosagem Antagonistas de Receptores de Angiotensina/efeitos adversos Antagonistas de Receptores de Angiotensina/farmacocinética Pressão Sanguínea/efeitos dos fármacos Bloqueadores dos Canais de Cálcio/administração & dosagem Método Duplo-Cego Monitoramento de Medicamentos/métodos Feminino Seres Humanos Hipertensão/diagnóstico Hipertensão/tratamento farmacológico Hipertensão/metabolismo Metabolismo dos Lipídeos/efeitos dos fármacos Metabolismo dos Lipídeos/fisiologia Masculino Meia-Idade Peptídeos Natriuréticos/metabolismo Neprilisina/antagonistas & inibidores Neprilisina/metabolismo Obesidade Abdominal/diagnóstico Obesidade Abdominal/tratamento farmacológico Obesidade Abdominal/metabolismo Tetrazóis/administração & dosagem Tetrazóis/efeitos adversos Tetrazóis/farmacocinética Resultado do Tratamento
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Aminobutyrates); 0 (Angiotensin Receptor Antagonists); 0 (Calcium Channel Blockers); 0 (LCZ 696); 0 (Natriuretic Peptides); 0 (Tetrazoles); 1J444QC288 (Amlodipine); EC 3.4.24.11 (Neprilysin) |
[Em] Mês de entrada: | 1712 |
[Cu] Atualização por classe: | 180207 |
[Lr] Data última revisão:
| 180207 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171129 |
[Cl] Clinical Trial: | ClinicalTrial
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[St] Status: | MEDLINE |
[do] DOI: | 10.1161/HYPERTENSIONAHA.117.10224 |
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