Egg white hydrolysate protects white adipose tissue against metabolic insult in deoxycorticosterone acetate-salt rats.

The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 2­3th week, and 6 mg/kg -4­8th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1ß), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.

ß-Adrenergic Stimulation-Induced PVAT Dysfunction in Male Sex: A Role for 11ß-Hydroxysteroid Dehydrogenase-1.

Long-term ß-adrenoceptor (ß-AR) stimulation is a pathological mechanism associated with cardiovascular diseases resulting in endothelial and perivascular adipose tissue (PVAT) dysfunction. In this study, we aimed to identify whether ß-adrenergic signaling has a direct effect on PVAT. Thoracic aorta PVAT was obtained from male Wistar rats and cultured ex vivo with the ß-AR agonist isoproterenol (Iso; 1 µM) or vehicle for 24 hours. Conditioned culture medium (CCM) from Iso-treated PVAT induced a marked increase in aorta contractile response, induced oxidative stress, and reduced nitric oxide production in PVAT compared to vehicle. In addition, Iso-treated PVAT and PVAT-derived differentiated adipocytes exhibited higher corticosterone release and protein expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), an enzyme responsible for de novo synthesis of corticosterone. Macrophages exposed to Iso also exhibited increased corticosterone release in response to ß-AR stimulation. Incubation of Iso-treated PVAT and PVAT-derived differentiated adipocytes with ß3-AR antagonist restored aorta contractile function modulated by Iso-CCM and normalized 11ß-HSD1 protein expression. These results show that ß3-AR signaling leads to upregulation of 11ß-HSD1 in PVAT, thus increasing corticosterone release and contributing to impair the anticontractile function of this tissue.

Pancreatic islets isolated from ß2 adrenergic receptor knockout mice show reduced insulin secretion in response to nutrients / Ilhotas pancreáticas isoladas de camundongos com deleção do receptor adrenérgico ß2 apresenta reduzida secreção de insulina em resposta a nutrientes

Activation of ß2 adrenergic receptors by catecholamine or catecholamine-mimetic substances may enhance insulin secretion. We herein investigated KCl- and nutrient-stimulated insulin secretion in pancreatic islets isolated from ß2 knockout (ß2KO) mice. ß2KO mice showed reduced body weight, fasting hypoglycaemia associate to a similar fasting insulinemia compared to control. ß2KO mice also showed reduced glucose tolerance despite the higher sensitivity to insulin. Glucose-induced insulin secretion was impaired in pancreatic islets isolated from ß2KO mice. Leucine-induced (20mM) insulin secretion was diminished in pancreatic islets isolated from ß 2KO mice when compared to control one. The depolarizing effect of KCl on insulin secretion was also impaired in pancreatic islets from ß2KO mice. These results suggested a possible role of ß2 adrenergic receptors on nutrient-induced insulin secretion.

A ativação dos receptores ß2-adrenérgicos por catecolaminas ou miméticos a catecolaminas podem aumentar a secreção de insulina. Nós investigamos a secreção de insulina estimulada por nutrients e KCl em ilhotas pancreáticas isoladas de camundongos com deleção dos receptores ß2-adrenérgicos (ß2KO). Camudongos ß2KO apresentaram reduzido peso corporal, hipoglicemia de jejum associada a semelhante concentração de insulina plasmática de jejum comparada ao grupo controle. Camundongos ß2KO apesar de apresentarem aumento da sensibilidade a insulina também apresentaram reduzida tolerância a glicose. A secreção de insulina induzida com glicose foi alterada em ilhotas pancreáticas isoladas de camundongos ß2KO. Secreção de insulina induzida por leucina (20mM) foi diminuída em ilhotas pancreáticas isoladas de camundongos ß2KO quando comparado ao controle. O efeito despolarizante do KCl sobre a secreção de insulina também foi alterado em ilhotas pancreáticas de camundongos ß2KO. Estes resultados sugerem um possível papel dos receptores ß2-adrenérgicos na secreção de insulina induzida por nutrientes.

Remodelamento miocárdico após grandes infartos converte potenciação pós-pausa em decaimento da força em ratos / Myocardial remodeling after large infarcts in rat converts post rest-potentiation in force decay / Miocárdio remodelado después de grandes infartos en ratas convierte potenciación post-pausa en disminucion de la fuerza

FUNDAMENTO: A Contração Pós-Repouso (CPR) do músculo cardíaco fornece informações indiretas sobre a manipulação de cálcio intracelular. OBJETIVO: Nosso objetivo foi estudar o comportamento da CPR e seus mecanismos subjacentes em camundongos com infarto do miocárdio. MÉTODOS: Seis semanas após a oclusão coronariana, a contratilidade dos Músculos Papilares (MP) obtidos a partir de camundongos submetidos à cirurgia sham (C, n = 17), com infarto moderado (MMI, n = 10) e grande infarto (LMI, n = 14), foi avaliada após intervalos de repouso de 10 a 60 segundos antes e depois da incubação com cloreto de lítio (Li+) em substituição ao cloreto de sódio ou rianodina (Ry). A expressão proteica de SR Ca(2+)-ATPase (SERCA2), trocador Na+/Ca2+ (NCX), fosfolambam (PLB) e fosfo-Ser (16)-PLB foi analisada por Western blotting. RESULTADOS: Os camundongos MMI apresentaram potenciação de CPR reduzida em comparação aos camundongos C. Em oposição à potenciação normal para camundongos C, foram observadas degradações de força pós-repouso nos músculos de camundongos LMI. Além disso, a Ry bloqueou a degradação ou potenciação de PRC observada em camundongos LMI e C; o Li+ inibiu o NCX e converteu a degradação em potenciação de CPR em camundongos LMI. Embora os camundongos MMI e LMI tenham apresentado diminuição no SERCA2 (72 ± 7% e 47 ± 9% de camundongos controle, respectivamente) e expressão protéica de fosfo-Ser16-PLB (75 ± 5% e 46 ± 11%, respectivamente), a superexpressão do NCX (175 ± 20%) só foi observada nos músculos de camundongos LMI. CONCLUSÃO: Nossos resultados mostraram, pela primeira vez, que a remodelação miocárdica pós-IAM em camundongos pode mudar a potenciação regular para degradação pós-repouso, afetando as proteínas de manipulação de Ca(2+) em miócitos.

BACKGROUND: Post-rest contraction (PRC) of cardiac muscle provides indirect information about the intracellular calcium handling. OBJECTIVE: Our aim was to study the behavior of PRC, and its underlying mechanisms, in rats with myocardial infarction. METHODS: Six weeks after coronary occlusion, the contractility of papillary muscles (PM) obtained from sham-operated (C, n=17), moderate infarcted (MMI, n=10) and large infarcted (LMI, n=14) rats was evaluated, following rest intervals of 10 to 60 seconds before and after incubation with lithium chloride (Li+) substituting sodium chloride or ryanodine (Ry). Protein expression of SR Ca(2+)-ATPase (SERCA2), Na+/Ca2+ exchanger (NCX), phospholamban (PLB) and phospho-Ser(16)-PLB were analyzed by Western blotting. RESULTS: MMI exhibited reduced PRC potentiation when compared to C. Opposing the normal potentiation for C, post-rest decays of force were observed in LMI muscles. In addition, Ry blocked PRC decay or potentiation observed in LMI and C; Li+ inhibited NCX and converted PRC decay to potentiation in LMI. Although MMI and LMI presented decreased SERCA2 (72±7% and 47±9% of Control, respectively) and phospho-Ser16-PLB (75±5% and 46±11%, respectively) protein expression, overexpression of NCX (175±20%) was only observed in LMI muscles. CONCLUSION: Our results showed, for the first time ever, that myocardial remodeling after MI in rats may change the regular potentiation to post-rest decay by affecting myocyte Ca(2+) handling proteins.

FUNDAMENTO: La Contracción pos pausa (CPP) del músculo cardíaco provee informaciones indirectas sobre la manejo del calcio intracelular. OBJETIVO: Nuestro objetivo fue estudiar el comportamiento de la CPP y sus mecanismos subyacentes en Ratas con infarto de miocardio. MÉTODOS: Seis semanas después de la oclusión coronaria, la contractilidad de los Músculos Papilares (MP) obtenidos a partir de Ratas sometidos a falsa cirurgia (C, n = 17), con infarto moderado (MMI, n = 10) y gran infarto (LMI, n = 14), fue evaluada después de pausas de estímulos de 10 a 60 segundos antes y después de la incubación con cloruro de litio (Li+) en substitución del cloruro de sodio o rianodina (Ry). La expresión proteica de SR Ca(2+)-ATPasa (SERCA2), intercambiador Na+/Ca2+ (NCX), fosfolamban (PLB) y fosfo-Ser (16)-PLB fue analizada por Western blotting. RESULTADOS: Los Ratas MMI presentaron potenciación de CPP reducida en comparación a los Ratas C. En oposición a la potenciación normal para Ratas C, fueron observadas decaimientos de fuerza post-reposo en los músculos de Ratas LMI. Además de eso, la Ry bloqueó la decaimiento o potenciación de PRC observada en Ratas LMI y C; el Li+ inhibió el NCX y convirtió la decaimiento en potenciación de CPP en Ratas LMI. Aunque los Ratas MMI y LMI hayan presentado disminución en el SERCA2 (72 ± 7% y 47 ± 9% de Ratas control, respectivamente) y expresión proteica de fosfo-Ser16-PLB (75 ± 5% y 46 ± 11%, respectivamente), la superexpresión del NCX (175 ± 20%) sólo fue observada en los músculos de Ratas LMI. CONCLUSIÓN: Nuestros resultados mostraron, por primera vez, que el remodelado miocárdico post-IAM en Ratas puede cambiar la potenciación regular para decaimiento post-reposo, afectando las proteínas de manejo del Ca(2+) en miocitos.