RESUMO
BACKGROUND: Cardiac anaphylaxis is one of the features of anaphylactic hypotension. Patients treated with propranolol, a nonselective ß-adrenoceptor (AR) antagonist, develop severe anaphylaxis, but the mechanism remains unknown. Under examination were the effects of ß1- and ß2-AR antagonist on anaphylaxis-induced coronary vasoconstriction and cardiac dysfunction in isolated blood-perfused rat hearts. METHODS: Isolated hearts from ovalbumin-sensitized Wistar rats were subjected to coronary perfusion with blood at a constant pressure and measurements were made of coronary blood flow and left ventricu-lar (LV) pressure. Following pretreatment with selective ß2-AR antagonist ICI118,551 or selective ß1-AR antagonist atenolol, cardiac anaphylaxis was induced by intracoronary injections of ovalbumin antigen. LV contractility was evaluated by the maximum increasing rate of systolic LV pressure (dP/dtmax). RESULTS: In response to antigen administrations, ICI118,551 pretreated hearts showed a greater de-crease in coronary blood flow and consequently a greater increase in coronary vascular resistance than the atenolol pretreated hearts. Pretreatment with ICI118,551 caused a greater decrease in dP/dtmax than those with atenolol. CONCLUSIONS: Cardiac anaphylaxis-induced contractile dysfunction and coronary spasm are severe in b2-, rather than ß1-AR antagonist, pretreated isolated blood-perfused rat hearts.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/toxicidade , Antagonistas de Receptores Adrenérgicos beta 2/toxicidade , Anafilaxia/induzido quimicamente , Atenolol/toxicidade , Vasoespasmo Coronário/induzido quimicamente , Vasos Coronários/efeitos dos fármacos , Propanolaminas/toxicidade , Vasoconstrição/efeitos dos fármacos , Disfunção Ventricular Esquerda/induzido quimicamente , Função Ventricular Esquerda/efeitos dos fármacos , Anafilaxia/metabolismo , Anafilaxia/fisiopatologia , Animais , Vasoespasmo Coronário/metabolismo , Vasoespasmo Coronário/fisiopatologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Preparação de Coração Isolado , Masculino , Contração Miocárdica/efeitos dos fármacos , Ovalbumina , Ratos Wistar , Receptores Adrenérgicos beta 1/efeitos dos fármacos , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Fatores de Tempo , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular/efeitos dos fármacosRESUMO
Beige adipocytes emerge postnatally within the white adipose tissue in response to certain environmental cues, such as chronic cold exposure. Because of its highly recruitable nature and relevance to adult humans, beige adipocytes have gained much attention as an attractive cellular target for antiobesity therapy. However, molecular circuits that preferentially promote beige adipocyte biogenesis remain poorly understood. We report that a combination of mild cold exposure at 17°C and capsinoids, a nonpungent analog of capsaicin, synergistically and preferentially promotes beige adipocyte biogenesis and ameliorates diet-induced obesity. Gain- and loss-of-function studies show that the combination of capsinoids and cold exposure synergistically promotes beige adipocyte development through the ß2-adrenoceptor signaling pathway. This synergistic effect on beige adipocyte biogenesis occurs through an increased half-life of PRDM16, a dominant transcriptional regulator of brown/beige adipocyte development. We document a previously unappreciated molecular circuit that controls beige adipocyte biogenesis and suggest a plausible approach to increase whole-body energy expenditure by combining dietary components and environmental cues.
