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1.
J Renin Angiotensin Aldosterone Syst ; 16(3): 481-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23950549

RESUMO

INTRODUCTION: adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor, and it has recently been suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating the AMPK system. This study aimed to evaluate the effects of candesartan, an angiotensin II receptor blocker, on cardiac and hepatic AMPK activity basally as well as after surgical stress under general anesthesia. MATERIALS AND METHODS: Male Wistar rats were treated with 5 mg/kg/day candesartan in their drinking water for two weeks. Levels of cardiac and hepatic AMPK activity were determined, using a kinase activity assay, basally and after surgical stress under general anesthesia. RESULTS: Chronic administration of candesartan increased hepatic AMPK activity approximately 4 times (p<0.05) while no significant change was demonstrated in cardiac AMPK. Cardiac and hepatic AMPK activities were not significantly increased by surgical stress alone performed under anesthesia. However, chronic treatment with candesartan decreased AMPK activity in both liver and heart after surgical stress under anesthesia (p<0.01 for both comparisons). CONCLUSIONS: While chronic candesartan treatment may stimulate AMPK activity in certain organs such as the liver, when combined with surgical stress under anesthesia it inhibits pathways regulating AMPK activity.


Assuntos
Adenilato Quinase/metabolismo , Benzimidazóis/farmacologia , Laparotomia , Fígado/enzimologia , Miocárdio/enzimologia , Estresse Fisiológico , Tetrazóis/farmacologia , Animais , Benzimidazóis/administração & dosagem , Compostos de Bifenilo , Fígado/efeitos dos fármacos , Masculino , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos , Tetrazóis/administração & dosagem
2.
Stress ; 15(5): 554-61, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22217206

RESUMO

5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Hipotálamo/efeitos dos fármacos , Estresse Fisiológico , Tetrazóis/farmacologia , Animais , Compostos de Bifenilo , Hipotálamo/metabolismo , Masculino , Ratos , Ratos Wistar , Sistema Renina-Angiotensina/efeitos dos fármacos
3.
Crit Care ; 15(5): R245, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22018099

RESUMO

INTRODUCTION: We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. METHODS: We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. RESULTS: Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. CONCLUSIONS: Unlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.


Assuntos
Tecido Adiposo/química , Estado Terminal , Ativação de Macrófagos , Macrófagos/química , Tecido Adiposo/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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