EFEITOS DA ANGIOTENSINA II NO SISTEMA CARDIOVASCULAR

Angiotensin is an important peptide of renin-angiotensin-aldosterone system. This peptide has an important function on arterial blood pressure regulation and body fluid homeostasis. However, its action on abnormal conditions causes deleterious effects on the cardiovascular system. Vascular resistance, hypertension, vascular and myocytes hipertrophy, production of free radicals and pro-inflammatory substances are some of the actions of angiotensin II that can result on cardiovascular remodeling. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptors antagonists, antiinflammatories and antioxidants are used clinically and/or experimentally to prevent or reduce the effects of angiotensin II. The purpose of this work is to review the actions and interactions of angiotensin II on the cardiovascular system, as well as the therapeutic measures employed for the control of these effects.La angiontesina II es el principal péptido del sistema renina-angiotensina-aldosterona. Este péptido tiene un papel importante en la regulación de la presión sanguínea y la homeostasis de los líquidos corporales. Sin embargo, su actuación en condiciones anormales genera efectos en detrimento del sistema cardiovascular. La resistencia vascular, hipertensión, hipertrofia del miocitos, así como el estímulo de la producción de radicales libres y sustancias pro-inflamatorias son algunos de los efectos de la angiotensina II que pueden llevar a la denominada remodelación cardiovascular. Los inhibidores ECA, los antagonistas de los receptores de angiotensina, los antiinflamatorios y los antioxidantes son utilizados clínica y/o experimentalmente para prevenir o reducir los efectos de la angiotensina II. Este trabajo tiene como objetivo revisar en la literatura las acciones e interacciones del péptido angiotensina II en el sistema cardiovascular, así como las expectativas terapéuticas empleadas para el control de sus efectos.A angiotensina II é um importante peptídeo do sistema renina-angiotensina-aldosterona (SRAA). Esse peptídeo tem um papel importante na regulação da pressão sanguínea e homeostase dos fluidos corporais. Contudo, a sua atuação em condições anormais gera efeitos deletérios ao sistema cardiovascular. Resistência vascular, hipertensão, hipertrofia de miócitos, estímulo à produção de radicais livres e substâncias pró-inflamatórias são algumas das ações da angiotensina II que podem resultar no evento denominado de remodelação cardiovascular. Inibidores da enzima conversora de angiotensina (ECA), antagonistas dos receptores de angiotensina, anti-inflamatórios e anti-oxidantes são utilizados clínica e/ou experimentalmente para prevenir ou reduzir os efeitos da angiotensina II. Este trabalho tem como objetivo rever na literatura as ações e interações do peptídeo angiotensina II no sistema cardiovascular. Assim como, as possibilidades terapêuticas empregadas para o controle dos seus efeitos

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts benefi cial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril). Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fi brillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to each variable depending on worsening of clinical evaluation (history and physical exam, QoLQ and echocardiogram (echo).Three dogs died during treatment due to worsening of HF, one of PL group and two of DIG group; furthermore, one of PIMO group was censored due to worsening of heart failure. There was no signifi cant difference between and within groups for echo and radiography. PL and DIG groups did not show any signifi cant difference throughout the 28 days of treatment. PIMO group showed lower physical exam score and increased early mitral infl ow velocity on day 28. Serum creatinine increased on days 14 and 28 compared to baseline, but within normal limits. The groups were similar within each evaluation day. Discussion: This is the fi rst short term prospective randomized double blind study comparing PIMO to DIG or PL additionally to conventional therapy (ACEi and furosemide) for dogs with HF due to CDMVD. It was observed an early signifi cant clinical improvement in dogs receiving PIMO compared to those receiving DIG or PL. The increase in early mitral infl ow velocity (E-wave) on day 28 for PIMO group is suggestive of diastolic dysfunction improvement, but this is only one variable related to diastolic function. Creatinine concentration increased in PIMO group, although it remained within normal range. In the present study, although all the three groups received furosemide, only PIMO group showed increase in blood creatinine between baseline and days 7 and 28. This result must be explored in later studies. Regarding the exercise intolerance assessment in a QoLQ, it must be aware that the owner evaluation is strongly infl uenced by the level of exercise that the dog is regularly submitted. Considering that most of the times, small breed dogs in a more advanced age is probably more sedentary and this fact surely precludes the owner to assess the exercise capacity. A more objective evaluation of the exercise tolerance should be considered in further clinical trials. Probably because of the small number of animals included in this study, differences in other studied variables were not found. The short-term follow-up of these patients may also have infl uenced the lack of differences among groups. Considering that stronger clinical evidence is needed to guide clinical decisions, longer prospective studies are also needed to compare the effects of DIG and PIMO, as well as to consider the benefi ts of the use or not of DIG associated with PIMO for dogs in HF due to CDMVD.Funding. This project was fi nancially supported by FAPESP - São Paulo Research Foundation, process number 08/57620-2

Nanomateriais - o que são, que riscos comportam

Aula 6: Nanomateriais - o que são, que riscos comportam. Nanomaterials (NM) – Materials with one or more components that have at least one dimension in the range of 1 to 100 nmN/

O papel da ciclooxigenase-2 da pressão arterial na lesão renal de ratos submetidos à infusão contínua de angiotensina II

Angiotensin II (ANGII) is a vasoconstrictor which action on inflammation has been studied. The objective of this study was to verify the stimulation of cyclooxigenase-2 and blood pressure on renal damage by ANGII. Wistar rats were distributed into four groups, as follows: group 1 – control; group 2 – ANGII; group 3 – ANGII + celecoxib; and group 4 – celecoxib. The ANGII was infused in the animals by subcutaneous osmotic mini-pumps during 72 hours. After that, euthanasia was performed. The blood pressure was measured before the drugs administration and before the euthanasia. Histopathological and immunohistochemical evaluations were performed in kidneys to assess the expression of COX-2. It was concluded that ANGII caused renal damage, regardless of blood pressure values. ANGII associated with celeboxib increased blood pressure. Celecoxib did not protect the kidneys against ANGII activities.A angiotensina II (ANGII) é um vasoconstritor, entretanto, sua atuação na inflamação tem sido estudada. Objetivou-se verificar o estímulo da ciclooxigenase-2 e da pressão arterial na lesão renal por ANGII. Para tanto, utilizaram-se ratos Wistar, distribuídos no grupo 1: controle, grupo 2: ANGII, grupo 3: ANGII + celecoxibe, grupo 4: celecoxibe. A ANGII foi administrada via minibomba no subcutâneo dos animais durante 72 horas, sendo então realizada a eutanásia. A pressão arterial foi aferida antes da administração dos fármacos e antes da eutanásia. Colheram-se os rins dos animais para histopatologia e para imunoistoquímica, avaliando-se a expressão de COX-2. Concluiu-se que a ANGII promoveu lesões renais, independentemente dos valores da pressão arterial; ANGII associada ao celecoxibe levou ao aumento da pressão arterial. O celecoxibe não protegeu os rins contra as ações da angiotensina II.Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Surveillance for zoonotic vector-borne infections using sick dogs from southeastern Brazil

For many vector-borne organisms, dogs can be used as sentinels to estimate the risk of human infection. The objective of this study was to use dogs as sentinels for multiple vector-borne organisms in order to evaluate the potential for human infection with these agents in southeastern Brazil. Blood from 198 sick dogs with clinicopathological abnormalities consistent with tick-borne infections were selected at the São Paulo State University Veterinary Teaching Hospital in Botucatu and tested for DNA and/or antibodies against specific vector-borne pathogens. At least one organism was detected in 88% of the dogs, and Ehrlichia canis DNA was amplified from 78% of the blood samples. Bartonella spp. seroreactivity was found in 3.6%. Leishmania chagasi antibodies were detected in 1% of the dogs. There was no serological or polymerase chain reaction evidence of infection with Anaplasma phagocytophilum, Borrelia burgdorferi, Ehrlichia chaffeensis, Ehrlichia ewingii, and Rickettsia rickettsii. The full E. canis 16S rRNA gene sequence of one of the Brazilian strains obtained in this study was identical to the causative agent of human ehrlichiosis in Venezuela. Ehrlichia canis may pose a human health hazard and may be undiagnosed in southeastern Brazil, whereas exposure to the other organisms examined in this study is presumably infrequent

Lesão vascular mediada pelo receptor AT1 esses efeitos em miocárdio, rins e fígado de ratos

The systemic aspect of vascular damage induced by angiotensin II (ANG II) has been poorly explored in the literature. Considering the presence of ANG II and its specific receptor AT1, in several organs, all tissues might be potentially affected by its effects. The aims of this study were: To evaluate the early histological changes in the heart, liver and kidneys, produced by ANG II infusion, to evaluate the protective effect of losartan. Wistar rats were distributed into three groups: control (no treatment), treated with ANG II, and treated with ANG II + losartan. ANG II was continuously infused over 72 hours by subcutaneous osmotic pumps. Histological sections of the myocardium, kidneys and liver were stained and observed for the presence of necrosis. There were ANG II-induced perivascular inflammation and necrosis of the arteriolar wall in the myocardium, kidney, and liver by, which were partially prevented by losartan. There was no significant correlation between heart and kidney damage. Tissue lesion severity was lower than that of vascular lesions, without statistical difference between groups. ANG II causes vascular injury in the heart, kidneys and liver, indicating a systemic vasculotoxic effect; the mechanisms of damage/protection vary depending on the target organ; perivascular lesions may occur even when anti-hypertensive doses of losartan are used.O aspecto sistêmico da lesão vascular induzida pela angiotensina II (ANG II) tem sido pouco explorada na literatura. Considerando a presença de ANG II e de seu receptor AT1 em diversos órgãos, todos os tecidos poderiam ser potencialmente afetados por esses efeitos. Os objetivos deste estudo foram: avaliar as alterações histológicas iniciais no coração, fígado e rins, produzidas pela infusão de ANG II, e avaliar o efeito protetor do losartan. Ratos Wistar foram divididos em três grupos: controle (sem tratamento), tratados com ANG II, e tratados com ANG II + losartan. A ANG II foi infundida continuamente por 72 horas por meio de mini-bombas osmóticas. Foram realizados cortes histológicos de miocárdio, rim e fígado para coloração e observação para a presença de necrose. Observou-se a presença de inflamação perivascular e necrose de parede arteriolar em miocárdio, rins e fígado, que foram parcialmente prevenidas pelo losartan. Não houve correlação significante entre as lesões observadas no coração e nos rins. A severidade da lesão tissular foi menor quando comparada às lesões vasculares, sem diferença estatística entre os grupos. A ANG II causa injúria vascular no coração, rins e fígado, sugerindo um efeito vasculotóxico sistêmico; os mecanismos de lesão/proteção variam dependendo do órgão afetado; as lesões perivasculares podem ocorrer mesmo quando doses antihipertensivas de losartan forem utilizadas

Displasia valvar tricúspide em um felino doméstico: relato de caso

Tricuspid valve dysplasia (TVD) is a congenital heart defect described in dogs and cats; however, in Brazil there are no reports of this condition in cats. Therefore, our goal was to report a case of TVD in a domestic cat. A four-year-old, female, domestic short hair cat that was seen at the Cardiology Service of the Veterinary Teaching Hospital, University of São Paulo, for apathy, appetite loss and dyspnea for five days. During physical examination, dyspnea with a restrictive respiratory pattern due to pleural effusion was observed. Thoracocentesis was performed and 450 mL of serosanguineous fluid was drained. Two-dimensional echocardiography in the right parasternal short-axis plane at the level of the papillary muscles showed right ventricular dilatation and paradoxical septal motion. On the left parasternal apical four-chamber view, significant dilatation of the right chambers, loss of mobility of the septal leaflet of the tricuspid valve and a thickened mural leaflet chordae with anomalous insertion were observed. Based on clinical and echocardiographic aspects, a diagnosis of TVD was given. Treatment was initiated with enalapril 0.5 mg/kg, furosemide 0.5 mg/kg and pimobendan 0.3 mg/kg every 12 hours, all per os. The patient experienced remission of clinical manifestations and survived for 50 days after diagnosis.Displasia valvar tricúspide (DVT) é um defeito cardíaco congênito descrito em cães e gatos. Entretanto no Brasil ainda não há relato desta cardiopatia em felinos. Desta forma, objetivou-se relatar um caso de DVT em um felino doméstico. Uma gata de pelo curto, com quatro anos de idade foi atendida no Serviço de Cardiologia do Hospital Veterinário da Universidade de São Paulo, apresentando apatia, perda de apetite e dispneia há cinco dias. Durante o exame físico observou-se dispneia com padrão respiratório restritivo devido a presença de efusão pleural. Foram drenados 450 mL de líquido serosanguinolento por meio de toracocentese. O ecocardiograma no modo bidimensional, pela janela paraesternal direita, ao eixo curto transversal ao nível dos músculos papilares, revelou hipertrofia excêntrica do ventrículo direito e movimento septal paradoxal. Pela vista apical quatro câmaras, na janela paraesternal esquerda, observou-se importante remodelamento de câmaras cardíacas direitas. A valva tricúspide apresentou-se com perda de mobilidade de sua cúspide septal e espessamento de cordoalha tendínea da cúspide mural, com inserção anômala. Com base nos aspectos clínicos e ecocardiográficos, instituiu-se o dianóstico de DVT. Iniciou-se o tratamento com enalapril (0,5 mg/kg), furosemida (0,5 mg/kg) e pimobendan (0,3 mg/kg), pela via oral a cada 12 horas. O paciente apresentou remissão das manifestações clínicas, sobrevivendo por 50 dias após o diagnóstico