Role of Beta-adrenergic Receptors and Sirtuin Signaling in the Heart During Aging, Heart Failure, and Adaptation to Stress.

In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (ß-ARs), mainly the beta 1 (ß1-AR) and beta 2 (ß2-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The ß2-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 ß1/ß2-AR ratio and activation of the ß2-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-α, and nuclear factor-kappa B. In the heart, SIRT1, SIRT3, and ß2-ARs are crucial to the regulation of the cardiomyocyte energy metabolism, oxidative stress, reactive oxygen species production, and autophagy. SIRT1 and the ß2-AR-Gi complex also control signaling pathways of cell survival and death. Here, we review the role played by ß2-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.

BEEF TALLOW AND EMULSIFIER IN GROWING-FINISHING PIG DIETS.

Two trials were aimed to evaluate beef tallow in diets with and without emulsifier on performance of pigs at growing-finishing phases. In the first trial, 15 barrows (22.03±0.62 kg) were distributed among three treatments: reference diet; test diet 1 (5% beef tallow) and test diet 2 (10% beef tallow). Beef tallow presented average value of 7130.97 kcal ME/kg. For the performance trail, 30 barrows (24.85±1.18 kg) were distributed among five treatments: T1 - diet with soybean oil and 3230 kcal ME /kg; T2 - diet with beef tallow and 3230 kcal ME/kg; T3 - diet with beef tallow and 3080 kcal ME/kg; T4 - diet with beef tallow, 3080 kcal/kg and 0.1% emulsifier; T5 - diet with beef tallow, 2930 kcal ME/kg and 0.1% emulsifier. Feed conversion was worse in animals fed diet with 3080 kcal ME/kg containing beef tallow and with 2930 kcal ME/kg with beef tallow and emulsifier. For economic availability, animals fed diet with beef tallow and 3230 kcal ME/kg and those fed diet with 3080 kcal ME/kg containing beef tallow and emulsifier, did not differ from animals fed diet with soybean oil, which enables the reduction up to 150 kcal ME/kg be compensated by emulsifier addition.

Effects of electroacupuncture on stress and anxiety-related responses in rats.

The aim of this work was to investigate if eletroacupuncture at PC6 would modulate the stress-induced anxiety-like behavior and the level of activation of several brain areas. Rats were distributed in groups: control; submitted to immobilization; submitted to immobilization and eletroacupuncture at PC6 or at the tail. Immobilization increased grooming and decreased stretched attend postures and the time spent in the open arms of the ele-vated plus-maze. Eletroacupuncture at PC6 or tail canceled the effect of immobilization on grooming and attenuated the stretched attend posture. Immobilization increased Fos-immunoreactivity in the prefrontal cortex, medial and central amygdala, paraventricular and dorsomedial nuclei of the hypothalamus, lateral hypothalamus, dentate gyrus, CA1, CA2 and CA3 hippocampal areas. The activation of paraventricular, dorsomedial nuclei and prefrontal cortex by immobilization was canceled by electroacupuncture at PC6 and attenuated by electroacupuncture in the tail. The activation of the other areas was canceled by electroacupuncture in PC6 or the tail. It is concluded that immobilization induced anxiety-like behavior that was moderately attenuated by eletroacupuncture with difference between the stimulation in PC6 or the rat tail. Eletroacupuncture showed specificity concerning to the attenuation of the effects of immobilization in the CNS areas related to the stress response, anxiety and cardiovascular system.

Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

Clozapine prevented social interaction deficits and reduced c-Fos immunoreactivity expression in several brain areas of rats exposed to acute restraint stress.

In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.

Stress-induced differential gene expression in cardiac tissue.

The stress response is adaptive and aims to guarantee survival. However, the persistence of a stressor can culminate in pathology. Catecholamines released as part of the stress response over activate beta adrenoceptors (ß-AR) in the heart. Whether and how stress affects the expression of components of the intracellular environment in the heart is still, however, unknown. This paper used microarray to analyze the gene expression in the left ventricle wall of rats submitted to foot shock stress, treated or not treated with the selective ß2-AR antagonist ICI118,551 (ICI), compared to those of non-stressed rats also treated or not with ICI, respectively. The main findings were that stress induces changes in gene expression in the heart and that ß2-AR plays a role in this process. The vast majority of genes disregulated by stress were exclusive for only one of the comparisons, indicating that, in the same stressful situation, the profile of gene expression in the heart is substantially different when the ß2-AR is active or when it is blocked. Stress induced alterations in the expression of such a large number of genes seems to be part of stress-induced adaptive mechanism.

Effects of electroacupuncture on stress and anxiety-related responses in rats

ABSTRACT The aim of this work was to investigate if eletroacupuncture at PC6 would modulate the stress-induced anxiety-like behavior and the level of activation of several brain areas. Rats were distributed in groups: control; submitted to immobilization; submitted to immobilization and eletroacupuncture at PC6 or at the tail. Immobilization increased grooming and decreased stretched attend postures and the time spent in the open arms of the ele-vated plus-maze. Eletroacupuncture at PC6 or tail canceled the effect of immobilization on grooming and attenuated the stretched attend posture. Immobilization increased Fos-immunoreactivity in the prefrontal cortex, medial and central amygdala, paraventricular and dorsomedial nuclei of the hypothalamus, lateral hypothalamus, dentate gyrus, CA1, CA2 and CA3 hippocampal areas. The activation of paraventricular, dorsomedial nuclei and prefrontal cortex by immobilization was canceled by electroacupuncture at PC6 and attenuated by electroacupuncture in the tail. The activation of the other areas was canceled by electroacupuncture in PC6 or the tail. It is concluded that immobilization induced anxiety-like behavior that was moderately attenuated by eletroacupuncture with difference between the stimulation in PC6 or the rat tail. Eletroacupuncture showed specificity concerning to the attenuation of the effects of immobilization in the CNS areas related to the stress response, anxiety and cardiovascular system.