Navegando por Palavras-chave "Adrenergic receptors"

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    Papel dos receptores beta2-adrenérgicos na proteção de arritmias cardíacas induzidas em camundongos normais e hiperlipidêmicos
    (Universidade Federal de São Paulo (UNIFESP), 2013-12-20) Ternes, Simone Correia [UNIFESP]; Spadari, Regina Celia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Hypercholesterolemia, hypertension and atherosclerosis are associated comorbidities with high incidence of cardiovascular events, including arrhythmias and sudden cardiac death. The genetic profile associated to a high fat diet can result in anatomical and functional cardiac changes that may lead to pathological events and remodeling of the β-adrenergic receptors population. The β1 and β2 adrenoceptor subtypes play different roles in regulating heart function and structure. While the β1 subtype plays pro-apoptotic and proarrhythmic effects mediated by its interaction with stimulatory G protein (Gs), β2 adrenoceptors play the opposite effect by coupling with inhibitory G protein (Gi). Thus, in vivo receptors activation or inactivation by drugs and simultaneous record electrocardiogram is an interesting method to evaluate its effects on cardiac rhythm and performance hemodynamic status. This study aims to evaluate in vivo the β-adrenoceptor subtypes involvement in the generation of cardiac arrhythmias in normal mice and mice treated with high-cholesterol diet. It also aims to develop a protocol for evaluation of these parameters in conscious mice. The results showed that feeding mice with high-cholesterol diet increased serum cholesterol concentrations, mean arterial blood pressure and heart rate, the autonomic modulation reversing on the heart, increasing responsiveness to the positive chronotropic effect of isoproterenol and to the blocking effect of the β2 adrenergic antagonist ICI118.551. Furthermore, it induced arrhythmia that was accentuated by the β2 adrenoceptor blockade. It is concluded that the present data show that feeding high-cholesterol diet induced hemodynamic changes and heart rhythm disturbances. Moreover, this data reinforce the specificity of roles played by both adrenoceptor subtypes in the generation and protection cardiac arrhythmias, showing a possible protective anti-arrhythmic role played by β2 subtype and suggesting a compensatory or adaptive remodeling of β-adrenergic receptors population induced by stress and/or chronic overload imposed on the heart. We also conclude that this experimental model is suitable for the study cardiovascular physiology and of drugs effect on cardiovascular parameters in mice.
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    Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging, heart failure, and adaptation to stress
    (Springer/Plenum Publishers, 2018) Spadari, Regina Celia [UNIFESP]; Cavadas, Claudia; Carvalho, Ana Elisa Teofilo Saturi de [UNIFESP]; Ortolani, Daniela [UNIFESP]; Moura, Andre Luiz de [UNIFESP]; Vassallo, Paula Frizela; Universidade Federal de São Paulo (UNIFESP)
    In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (beta-ARs), mainly the beta 1 (beta(1)-AR) and beta 2 (beta(2)-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The beta(2)-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the beta(1)/beta(2)-AR ratio and activation of the beta(2)-AR-Gi-PI3K-Akt signaling pathway have been observed. Recent studies have shown that sirtuins modulate certain organic processes, including the cellular stress response, through activation of the PI3K-Akt signaling pathway and of downstream molecules such as p53, Akt, HIF1-alpha, and nuclear factor-kappa B. In the heart, SIRT1, SIRT3, and beta(2)-ARs are crucial to the regulation of the cardiomyocyte energy metabolism, oxidative stress, reactive oxygen species production, and autophagy. SIRT1 and the beta(2)-AR-Gi complex also control signaling pathways of cell survival and death. Here, we review the role played by beta(2)-ARs and sirtuins during aging, heart failure, and adaptation to stress, focusing on the putative interplay between the two. That relationship, if proven, merits further investigation in the context of cardiac function and dysfunction.