SummaryThe left ventricular hypertrophy (LVH) occurs in response to the hemodynamic overload in some physiological and pathological conditions. However, it has not been completely elucidated whether the primary stimulation for the hypertrophy is the mechanical stretching of the heart, neurohumoral factors, or even the interaction of both. These factors are translated inside the cell as biochemical alterations that lead to the activation of second (cytosolic) and third (nuclear) messengers that will act in the cell nucleus, regulating transcription, and will finally determine the genic expression that induces LVH. The LVH is characterized by structural alterations due to the increase in the cardiomyocyte dimensions, the proliferation of the interstitial connective tissue and the rarefaction of the coronary microcirculation. Recently, nitric oxide (• NO) has appeared as an important regulator of cardiac remodeling, specifically recognized as an anti-hypertrophic mediator. Some studies have demonstrated the cellular targets, the anti-hypertrophic signaling pathways and the functional role of• NO. Thus, the LVH seems to develop as a result of the loss of the balance between the pro and the antihypertrophic signaling pathways. This new knowledge about the pro and anti-hypertrophic signaling pathways will allow the development of new strategies in the treatment of pathological LVH.
High HDL plasma levels are a protective factor against the development of cardiovascular inflammation and insulin resistance in LDLr-/- mice, preventing the development of neointimal lesions.
Many studies have confirmed the merits of metformin to treat type 2 diabetes, but few studies have addressed its effect on the respiratory system. Moreover, vascular endothelial growth factor (VEGF) is critical to many lung functions. In this way, we evaluated the metformin impact on the lung in treated obese Swiss mice, induced by postnatal overnutrition. Glucose and insulin were detected and the insulin resistance index (HOMA) was calculated; inflammatory cells and nitrite/nitrate concentration (NOx) was quantified from bronchoalveolar lavage, collagen and lung VEGF-a was analysed in the lung tissue and lung mechanics were evaluated by methacholine-induced bronchoconstriction. Values of glucose, insulin, HOMA; VEGF-a and collagen demonstrate the partial ability of metformin to improve the effects of obesity. However, metformin is ineffective in re-establishing the inflammation, shows no effects on NOx and does not restore bronchoconstriction in obese mice. In conclusion, metformińs beneficial effects on lung are questionable in the postnatal overnutrition model of obesity.
The aim of this study was to determine the effects of previous administration of metyrapone (met) on the acute lung injury (ALI) induced by caecal ligation and puncture (CLP) and to explore met's relationship with endogenous glucocorticoids (GCs) as measured by inflammatory, oxidative and functional parameters. One hundred and thirty-five Wistar rats were divided into three main groups: Control (Naïve), Sham and CLP. The animals received pretreatment one hour before surgery. The Naïve group did not undergo any procedure or pretreatment. The Sham group only had the caecum exposed and was pretreated with saline. The CLP group was divided into three pretreatments: metyrapone (CLP met 50 mg/kg i.p.), dexamethasone (CLP dex 0.5 mg/kg i.p.) or saline (CLP sal equivalent volume of 0.9% NaCl). Analyses were performed after 6 and 24 h of sepsis. Previous administration of met significantly increased inflammatory cells, as well as myeloperoxidase (MPO) activity in the lung tissue and alveolar collapsed area, with consequent impairment of respiratory mechanics being observed compared to Sham and Naïve; CLP sal exhibited similar results to those of met. The met reduced corticosterone (CCT) levels and dramatically increased hydrogen peroxide (H2 O2 ) levels in the lung tissue compared to CLP sal. Our results suggest that previous administration of met may have contributed to increased pulmonary oxidative stress and increased mortality by mechanisms dependent of endogenous GC.
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