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J Cardiovasc Pharmacol ; 66(4): 399-408, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26222991

RESUMO

BACKGROUND: Enhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown. METHODS: We assessed in Zucker fa/fa rats, a rat model of MS, the cardiovascular effects of HRR induced by the If current inhibitor S38844 (3 mg · kg(-1) · d(-1)). RESULTS: Delayed short-term (4 days) and long-term (90 days) HRR induced by S38844 reduced LV end-diastolic pressure and LV end-diastolic pressure-volume relation, increased myocardial tissue perfusion, decreased myocardial oxidized glutathione levels, and preserved cardiac output, without modifying LV end-systolic pressure and LV end-systolic pressure-volume relation, although only long-term S38844 opposed LV collagen accumulation. Long-term S38844 improved flow-induced endothelium-dependent dilatation of mesenteric arteries, while metabolic parameters, such as plasma glucose levels, and Hb1c, were never modified. CONCLUSIONS: In rats with MS, HRR induced by the If inhibitor S38844 improved LV diastolic function and endothelium-dependent vascular dilatation, independent from modifications in metabolic status. Moreover, this improvement in cardiac function involves not only immediate effects such as improved myocardial perfusion and reduced oxidative stress but also long-term effects such as modifications in the myocardial structure.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Fármacos Cardiovasculares/administração & dosagem , Diástole/efeitos dos fármacos , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Canais Iônicos/antagonistas & inibidores , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Zucker , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
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