RESUMO
AIM: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipocytokine with insulin-sensitizing activity originally identified in visceral adipose tissues of obesity-related type II diabetic rats. We previously showed that vaspin inhibits vascular cell migration and apoptosis as well as inflammatory responses, which are crucial for the development of hypertension. However, little is known about the effects of vaspin on vascular reactivity. The aim of this study was thus to explore the effects of vaspin on contraction and relaxation of isolated blood vessel. METHODS: After mesenteric arteries were isolated from male Wistar rats, the effects of pretreatment with vaspin (3 ng mL(-1) , 30 min) on concentration-contraction and concentration-relaxation relationships for each agent were examined. The effects of vaspin on acetylcholine (ACh)-induced phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and ACh esterase (AChE) activity were also examined using Western blotting and colorimetric method respectively. RESULTS: Vaspin did not affect noradrenaline- or 5-hydroxytryptamine-induced contraction. In contrast, vaspin augmented ACh- but not histamine-, A23187- or carbachol-induced NO-mediated relaxation. Vaspin significantly increased ACh-induced eNOS phosphorylation and inhibited AChE activity. CONCLUSION: We for the first time demonstrate that vaspin augments the ACh-induced NO-mediated endothelium-dependent relaxation via the inhibition of AChE activity.
Assuntos
Acetilcolinesterase/metabolismo , Artérias Mesentéricas/metabolismo , Relaxamento Muscular/fisiologia , Músculo Liso Vascular/metabolismo , Serpinas/metabolismo , Acetilcolina/farmacologia , Animais , Western Blotting , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Ratos WistarRESUMO
AIM: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a relatively novel adipocytokine with protective effects on metabolic diseases including obesity and type II diabetes. We have previously demonstrated that vaspin exerts anti-inflammatory and antimigratory roles through antioxidative effects in vascular smooth muscle cells. As inflammatory responses and migration of smooth muscle in peripheral vascular wall are key mechanisms for the pathogenesis of hypertension, we hypothesized that vaspin could prevent the development of hypertension in in vivo hypertensive animal model. METHODS: Vaspin (1 µg kg(-1) day(-1) ) was administered intraperitoneally to 5-week-old male spontaneously hypertensive rats (SHR) for 4 weeks. Superior mesenteric artery was isolated and used for measurement of isometric contraction and histological analysis. RESULTS: Long-term vaspin treatment significantly prevented an elevation of systolic blood pressure (SBP) at 8 weeks of age. Vaspin had no effect on reactivity of isolated mesenteric artery from SHR. In contrast, vaspin significantly inhibited mesenteric arterial wall hypertrophy in SHR. Moreover, vaspin significantly inhibited an increase of tumour necrosis factor-α expression and a production of reactive oxygen species in isolated mesenteric artery from SHR. CONCLUSION: This study for the first time demonstrates that vaspin prevents the increase of SBP in SHR through inhibiting peripheral vascular hypertrophy possibly via antioxidative and anti-inflammatory mechanisms.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Artéria Mesentérica Superior/fisiopatologia , Serpinas/administração & dosagem , Remodelação Vascular/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , Relação Dose-Resposta a Droga , Infusões Parenterais , Masculino , Artéria Mesentérica Superior/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacosRESUMO
AIM: Eukaryotic elongation factor 2 kinase (eEF2K), also known as calmodulin (CaM)-dependent protein kinase (CaMK) III, is a unique member of CaMK family protein. We have recently found that expression of eEF2K protein increased in mesenteric artery from spontaneously hypertensive rats. As pathogenesis of hypertension is in part regulated by vascular structural remodelling via proliferation and migration of vascular smooth muscle cells (SMCs), we tested the hypothesis that eEF2K controls SMCs proliferation and migration. METHODSAND RESULTS: In rat mesenteric arterial SMCs, an eEF2K inhibitor, A-484954 (10 µm), significantly inhibited platelet-derived growth factor (PDGF)-BB (10 ng mL(-1) )-induced SMCs proliferation as determined by a cell counting and bromodeoxyuridine incorporation assay. PDGF-BB (10 ng mL(-1) )-induced SMCs migration was significantly inhibited by A-484954 (10 µm) as determined by a Boyden chamber assay. A-484954 (10 µm) significantly inhibited PDGF-BB (10 ng mL(-1) )-induced phosphorylation of eEF2K, extracellular signal-regulated kinase (ERK), Akt, p38 and heat-shock protein (HSP) 27 as determined by Western blotting. It was confirmed that a CaM inhibitor, W-7 (50 µm), inhibited PDGF-BB (10 ng mL(-1) )-induced phosphorylation of eEF2K. In an ex vivo mesenteric arterial ring assay, 10% foetal bovine serum-induced SMCs outgrowth was significantly inhibited by A-484954 (10 µm). CONCLUSION: We for the first time revealed that eEF2K mediates PDGF-BB-induced SMCs proliferation and migration through activating ERK, Akt, p38 and HSP27 signals in a CaM-dependent manner. Our results suggest eEF2K as a novel pharmaceutical target for the prevention of hypertensive cardiovascular diseases.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quinase do Fator 2 de Elongação/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Quinase do Fator 2 de Elongação/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Hipertensão/tratamento farmacológico , Masculino , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Chaperonas Moleculares , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fator de Crescimento Derivado de Plaquetas/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ratos Wistar , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Sleep behavior has been related to both child and environmental factors, but the relative importance of these factors is not yet clear. This study was an examination of the relation of diurnal sleep patterns to perinatal risk, infant temperament, home environment, parenting stress, emotional support, and social class. Twenty-three adolescent and 23 single adult mothers and infants were assessed in the home at 4 and 12 months. Percent sleep during the night was most strongly related to parenting stress and variability of night sleep to emotional support. Emotional support mediated effects of stress at 4 months. Results support the value of clinical assessment of sleep behavior.