Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin-angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective ATI receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol induced systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P) H oxidase-mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT(1)-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. (c) 2012 Elsevier Inc. All rights reserved.

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

Caryocar brasiliense Camb. "pequi" is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

Tráfego veicular e mortalidade por doenças do aparelho circulatório em homens adultos

OBJETIVO: Analisar a associação entre indicadores de exposição à poluição por tráfego veicular e mortalidade por doenças do aparelho circulatório em homens adultos. MÉTODOS: Foram analisadas informações sobre vias e volume de tráfego no ano de 2007 fornecidas pela companhia de engenharia de tráfego local. Mortalidade por doenças do aparelho circulatório no ano de 2005 entre homens ≥ 40 anos foram obtidas do registro de mortalidade do Programa de Aprimoramento de Informações de Mortalidade do Município de São Paulo, SP. Dados socioeconômicos do Censo 2000 e informações sobre a localização dos serviços de saúde também foram coletados. A exposição foi avaliada pela densidade de vias e volume de tráfego para cada distrito administrativo. Foi calculada regressão (α = 5%) entre esses indicadores de exposição e as taxas de mortalidade padronizadas, ajustando os modelos para variáveis socioeconômicas, número de serviços de saúde nos distritos e autocorrelação espacial. RESULTADOS: A correlação entre densidade de vias e volume de tráfego foi modesta (r² = 0,28). Os distritos do centro apresentaram os maiores valores de densidade de vias. O modelo de regressão espacial de densidade de vias indicou associação com mortalidade por doenças do aparelho circulatório (p = 0,017). Não se observou associação no modelo de volume de tráfego. Em ambos os modelos – vias e volume de tráfego (veículos leves/pesados) – a variável socioeconômica foi estatisticamente signifi cante. CONCLUSÕES: A associação entre mortalidade por doenças do aparelho circulatório e densidade de vias converge com a literatura e encoraja a realização de mais estudos epidemiológicos em nível individual e com métodos mais acurados de avaliação da exposição.

Neural differentiation of rat aorta pericyte cells

Pericyte perivascular cells, believed to originate mesenchymal stem cells (MSC), are characterized by their capability to differentiate into various phenotypes and participate in tissue reconstruction of different organs, including the brain. We show that these cells can be induced to differentiation into neural-like phenotypes. For these studies, pericytes were obtained from aorta ex-plants of Sprague-Dawley rats and differentiated into neural cells following induction with trans retinoic acid (RA) in serum-free defined media or differentiation media containing nerve growth and brain-derived neuronal factor, B27, N2, and IBMX. When induced to differentiation with RA, cells express the pluripotency marker protein stage-specific embryonic antigen-1, neural-specific proteins beta 3-tubulin, neurofilament-200, and glial fibrillary acidic protein, suggesting that pericytes undergo differentiation, similar to that of neuroectodermal cells. Differentiated cells respond with intracellular calcium transients to membrane depolarization by KCl indicating the presence of voltage-gated ion channels and express functional N-methyl-D-aspartate receptors, characteristic for functional neurons. The study of neural differentiation of pericytes contributes to the understanding of induction of neuroectodermal differentiation as well as providing a new possible stem-cell source for cell regeneration therapy in the brain. (C) 2011 International Society for Advancement of Cytometry

Protective Effects of Human Amniotic Fluid Stem Cells in a Model of Aorta Allograft Vasculopathy in Rats

Background. Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid derived stem cells (hAFSCs), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, display immunomodulatory properties. hAFSCs express mesenchymal and embryonic markers, show high proliferation rates; however, they do not induce tumor formation, and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. Methods. Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into three groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n = 8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n = 8); and ALLO + hAFSC, ALLO rats treated with hAFSC (10(6) cells; n = 8). Histological analysis and immunohistochemistry were performed 30 days posttransplantation. Results. The ALLO group developed a robust aortic neointimal formation (208.7 +/- 25.4 gm) accompanied by a significant high number of ED1(+) (4845 +/- 841 cells/mm(2)) and CD43(+) cells (4064 +/- 563 cells/mm(2)), and enhanced expression of a-smooth muscle actin in the neointima (25 +/- 6%). Treatment with hAFSC diminished neointimal thickness (180.7 +/- 23.7 mu m) and induced a significant decrease of ED1(+) (1100 +/- 276 cells/mm(2)), CD43(+) cells (1080 +/- 309 cells/mu m(2)), and alpha-smooth muscle actin expression 8 +/- 3% in the neointima. Conclusions. These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.

Comparative analysis between ventricular and sinoatrial node vascularization in cats

Biasi C., Borelli V., Benedicto H.G., Pereira M.R., Favaron P.O. & Bombonato P.P. 2012. [Comparative analysis between ventricular and sinoatrial node vascularization in cats.] Analise comparativa entre a vascularizacao ventricular e do no sinoatrial em gatos. Pesquisa Veterinaria Brasileira 31(1): 78-82. Setor de Anatomia dos Animais Domesticos e Silvestres, Faculdade de Medicina Veterinaria e Zootecnia, Universidade de Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitaria, Sao Paulo, SP 05508-000, Brazil. E-mail: caiobiasi@usp.br The possible existence of interdependence in the blood nutrition of both atrial and ventricular territories has been a subject of concern to cardiologists, mainly related to vascularization of the sinoatrial node and its dependence on just one coronary artery or both, and its relation with the predominance of these vessels in the ventricular vascularization. Therefore, this research aimed evaluated the relation of blood irrigation of the sinoatrial node in relation to the coronary artery predominance in the ventricle vascularization. In doing so, we analyzed 30 hearts of cats without pedigree, males and females, adults of several ages. They were not carrying any heart problems. The hearts were injected by the thoracic aorta with Neoprene Latex 450, stained with red pigment, and then they were dissected. It was found that when there was a prevalence of ventricular vascularization of the left type (63.34%) the sinoatrial node irrigation was predominantly in the dependency of the Ramus proximalis atrii dextri (78.9%) or with less frequency by Ramus proximalis atrii sinister (21.1%). In the ventricular vascularization of the balanced type (33.34%), the pacemaker irrigation was in dependence more often of Ramus proximalis atrii dextri (80%) or with less frequency the nutrition of the sinoatrial node occurred by Ramus proximalis atril sinister (20%). In a single-case, we observed the ventricular vascularization of the right type (3.34%), the pacemaker nutrition was in an exclusive dependence of the Ramus intermedius atril dextri. These results suggest in this species there is no relationship between both the sinoatrial node irrigation and the type of ventricular vascularization, regardless of gender.

Nitric Oxide Synthase in Heart and Thoracic Aorta After Liver Ischemia and Reperfusion Injury: An Experimental Study in Rats

Objectives: We tested the effects of liver reperfusion in the immunohistochemical expression of nitric oxide synthase on the thoracic aorta and the heart. Materials and Methods: We randomized 24 male Wistar rats into 3 groups: (1) control; (2) R2 group, with 60 minutes of partial (70%) liver ischemia and 2 hours of global liver reperfusion; (3) and R6 group, with 60 minutes of partial liver ischemia and 6 hours of global liver reperfusion. Results: In the heart, there was little, diffuse immunohistochemical endothelial staining; immunohistochemical inducible nitric oxide synthase staining was expressed in the adventitia layer of intramyocardial vessels in both cases, with a time-dependent but not statistically significant increase. In the thoracic aorta, a time-dependent decrease in endothelial nitric oxide synthase expression in the muscular layer after reperfusion, which was statistically significant in R6 versus the control. Positive immunostaining for inducible nitric oxide synthase was seen in the muscular and endothelial layers, and this varied from moderate in the control group, to light in the endothelium in groups R2 and R6. Conclusions: We observed changes that may be implicated in heart injury and impairment of aortal tone after liver ischemia and reperfusion injury.

Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses

Hypertension is a disorder affecting millions worldwide, and is a leading cause of death and debilitation in the United States. It is widely accepted that during hypertension and other cardiovascular diseases the vasculature exhibits endothelial dysfunction; a deficit in the relaxatory ability of the vessel, attributed to a lack of nitric oxide (NO) bioavailability. Recently, the one electron redox variant of NO, nitroxyl anion (NO-) has emerged as an endothelium-derived relaxing factor (EDRF) and a candidate for endothelium-derived hyperpolarizing factor (EDRF). NO- is thought to exist protonated (HNO) in vivo, which would make this species more resistant to scavenging. However, no studies have investigated the role of this redox species during hypertension, and whether the vasculature loses the ability to relax to HNO. Thus, we hypothesize that aorta from angiotensin II (AngII)-hypertensive mice will exhibit a preserved relaxation response to Angeli's Salt, an HNO donor. Male C57B16 mice, aged 12-14 weeks were implanted with mini-osmotic pumps containing AngII (90 ng/min, 14 days plus high salt chow) or sham surgery. Aorta were excised, cleaned and used to perform functional studies in a myograph. We found that aorta from AngII-hypertensive mice exhibited a significant endothelial dysfunction as demonstrated by a decrease in acetylcholine (ACh)-mediated relaxation. However, vessels from hypertensive mice exhibited a preserved response to Angeli's Salt (AS), the HNO donor. To confirm that relaxation responses to HNO were maintained, concentration response curves (CRCs) to ACh were performed in the presence of scavengers to both NO and HNO (carboxy-PTIO and L-cys, resp.). We found that ACh-mediated relaxation responses were significantly decreased in aorta from sham and almost completely abolished in aorta from AngII-treated mice. Vessels incubated with L-cys exhibited a modest decrease in ACh-mediated relaxations responses. These data demonstrate that aorta from AngII-treated hypertensive mice exhibit a preserved relaxation response to AS, an HNO donor, regardless of a significant endothelial dysfunction. (C) 2011 Elsevier Ltd. All rights reserved,

Morphologic and biomechanical changes of thoracic and abdominal aorta in a rat model of cigarette smoke exposure

Background: Smoking is the most relevant environmental factor that affects the development of aortic aneurysm. Smokers have elevated levels of elastase activity in the arterial wall, which leads to weakening of the aorta. The aim of this study was to verify whether cigarette smoke exposure itself is capable of altering the aortic wall. Methods: Forty-eight Wistar rats were divided into 2-, 4-, and 6-month experimental periods and into 2 groups: smokers (submitted to smoke exposure at a rate of 40 cigarettes/day) and nonsmokers. At the end of the experimental periods, the aortas were removed and crosssectioned to obtain histologic specimens for light microscopic and morphometric analyses. The remaining longitudinal segments were stretched to rupture and mechanical parameters were determined. Results: A degenerative process (i.e., a reduction in elastic fibers, the loss of lamellar arrangement, and a reduction of smooth muscle cells) was observed, and this effect was proportional in intensity to the period of tobacco exposure. We observed a progressive reduction in the yield point of the thoracic aorta over time (P < 0.05). There was a decrease in stiffness (P < 0.05) and in failure load (P < 0.05) at 6 months in the abdominal aorta of rats in the smoking group. Conclusions: Chronic exposure to tobacco smoke can affect the mechanical properties of the aorta and can also provoke substantial structural changes of the arterial wall

Doenças respiratórias e fatores associados: estudo de base populacional em São Paulo, 2008-2009

OBJETIVO: Estimar a prevalência de bronquite aguda, rinite e sinusite em crianças e adolescentes e identificar fatores associados. MÉTODOS: Estudo transversal, de base populacional. Foi realizado inquérito domiciliar com 1.185 crianças e adolescentes de São Paulo, SP, de 2008 a 2009. Os participantes foram selecionados a partir de amostragem probabilística, estratificada por sexo e idade e por conglomerados em dois estágios. Para análise ajustada foi realizada regressão múltipla de Poisson. RESULTADOS: Dos entrevistados, 7,3% referiram bronquite aguda, 22,6% rinite e 15,3% sinusite. Após análise ajustada, associaram-se à bronquite aguda auto-referida: idade de zero a quatro anos (RP = 17,86; IC95%: 3,65;90,91), cinco a nove anos (RP = 37,04; IC95%: 8,13;166,67), dez a 14 anos (RP = 20,83; IC95%: 4,93;90,91), referir ter alergia (RP = 3,12; IC95%: 1,70;5,73), cor da pele preta/parda (RP = 2,29; IC95%: 1,21;4,35) e morar em domicílio com um a três cômodos (RP = 1,85; IC95%: 1,17;2,94); à rinite auto-referida: idade dez a 14 anos (RP = 2,77; IC95%: 1,60;4,78), 15 a 19 anos (RP = 2,58; IC95%: 1,52;4,39), referir ter alergia (RP = 4,32; IC95%: 2,79;6,70), referir ter asma (RP = 2,30; IC95%: 1,30;4,10) e morar em apartamento (RP = 1,70; IC95%: 1,06;2,73); à sinusite auto-referida: idade cinco a nove anos (RP = 2,44; IC95%: 1,09;5,43), dez a 14 anos (RP = 2,99; IC95%: 1,36;6,58), 15 a 19 anos (RP = 3,62; IC95%: 1,68;7,81), referir ter alergia (RP = 2,23; IC95%: 1,41;3,52) e apresentar obesidade (RP = 4,42; IC95%: 1,56;12,50). CONCLUSÕES: As doenças respiratórias foram mais prevalentes em grupos populacionais com características definidas, como grupo etário, doenças auto-referidas, tipo de moradia e obesidade.

Doenças crônicas não transmissíveis no Brasil: prioridade para enfrentamento e investigação

As Doenças Crônicas Não Transmissíveis representam a maior carga de morbimortalidade no Brasil. Em 2011, o Ministério da Saúde lançou seu Plano de Ações Estratégicas para o Enfrentamento das Doenças Crônicas Não Transmissíveis, enfatizando ações populacionais para controlar as doenças cardiovasculares, diabetes, câncer e doença respiratória crônica, predominantemente pelo controle do fumo, inatividade física, alimentação inadequada e uso prejudicial de álcool. Apesar da produção científica significativa sobre essas doenças e seus fatores de risco no Brasil, poucos são os estudos de coorte nessa temática. Nesse contexto, o Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil) acompanha 15.105 servidores públicos do País. Seus dados espelham a realidade brasileira de altas prevalências de diabetes e hipertensão e dos fatores de risco. A diversidade das informações produzidas permitirá aprofundar o entendimento causal dessas doenças e subsidiar políticas públicas para seu enfrentamento.

Associação entre doenças imunológicas e suas manifestações clínicas semelhantes

Trata-se de um caso de uma paciente de 30 anos do sexo feminino, com prótese biológica valvar mitral em razão de estenose mitral sintomática e antecedentes de infarto agudo do miocárdio, episódios de convulsões tônico-clônicas generalizadas, alucinações visuais, eventos tromboembólicos cerebrais, apresentando no momento coreia e cardite aguda. Foram diagnosticados na paciente febre reumática em atividade, lúpus eritematoso sistêmico e síndrome do anticorpo antifosfolipídeo. A combinação de três diagnósticos incomuns em um mesmo paciente torna esse caso único, modificando o tratamento e seu prognóstico.