Katia Colombo Marchi

Hypertension and chronic ethanol consumption: What do we know after a century of study?

The influences of life habits on the cardiovascular system may have important implications for public health, as cardiovascular diseases are among the leading causes of shorter life expectancy worldwide. A link between excessive ethyl alcohol (ethanol) consumption and arterial hypertension was first suggested early last century. Since then, this proposition has received considerable attention. Support for the concept of ethanol as a cause of hypertension derives from several epidemiologic studies demonstrating that in the general population, increased blood pressure is significantly correlated with ethanol consumption. Although the link between ethanol consumption and hypertension is well established, the mechanism through which ethanol increases blood pressure remains elusive. Possible mechanisms underlying ethanol-induced hypertension were proposed based on clinical and experimental observations. These mechanisms include an increase in sympathetic nervous system activity, stimulation of the renin-angiotensin-aldosterone system, an increase of intracellular Ca(2+) in vascular smooth muscle, increased oxidative stress and endothelial dysfunction. The present report reviews the relationship between ethanol intake and hypertension and highlights some mechanisms underlying this response. These issues are of interest for the public health, as ethanol consumption contributes to blood pressure elevation in the population.

Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress

Abstract We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B2 (stable TXA2 metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H2O2) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

NADPH Oxidase Plays a Role on Ethanol-Induced Hypertension and Reactive Oxygen Species Generation in the Vasculature

AIMS Investigate the role of NADPH oxidase on ethanol-induced hypertension and vascular oxidative stress. METHODS Male Wistar rats were treated with ethanol (20% v/v). RESULTS Apocynin (10 mg/kg/day, i.p.) prevented ethanol-induced hypertension. The increased contractility of endothelium-intact and endothelium-denuded aortic rings from ethanol-treated rats to phenylephrine was prevented by apocynin. Ethanol consumption increased superoxide anion (O2 (-)) generation and lipid peroxidation and apocynin prevented these responses. The decrease on plasma and vascular nitrate/nitrite (NOx) levels induced by ethanol was not prevented by apocynin. Treatment with ethanol did not affect aortic levels of hydrogen peroxide (H2O2) or reduced glutathione (GSH). Ethanol did not alter the activities of xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol increased the expression of Nox1, PKCδ, nNOS, SAPK/JNK and SOD2 in the rat aorta and apocynin prevented these responses. No difference on aortic expression of Nox2, Nox4, p47phox, Nox organizer 1 (Noxo1), eNOS and iNOS was detected after treatment with ethanol. Ethanol treatment did not alter the phosphorylation of SAPK/JNK, p38MAPK, c-Src, Rac1 or PKCδ. CONCLUSIONS The major new finding of our study is that the increased vascular generation of reactive oxygen species (ROS) induced by ethanol is related to increased vascular Nox1/NADPH oxidase expression. This mechanism is involved in vascular dysfunction and hypertension induced by ethanol. Additionally, we conclude that ethanol consumption induces the expression of different proteins that regulate vascular contraction and growth and that NADPH oxidase-derived ROS play a role in such response. SHORT SUMMARY The key findings of our study are that ethanol-induced hypertension is mediated by NADPH oxidase. Moreover, increased vascular Nox1 expression is related to the generation of reactive oxygen species (ROS) by ethanol. Finally, ROS induced by ethanol increase the expression of the regulatory vascular proteins.

Vascular Oxidative Stress: A Key Factor in the Development of Hypertension Associated with Ethanol Consumption

The observation that the excessive consumption of ethyl alcohol (ethanol) is associated with high blood pressure is nearing its centennial mark. Mechanisms linking ethanol consumption and hypertension are complex and not fully understood. It is established that chronic ethanol consumption leads to hypertension and that this process is a multimediated event involving increased sympathetic activity, stimulation of the renin-angiotensin-aldosterone system with a subsequent increase in vascular oxidative stress and endothelial dysfunction. Under physiological conditions, reactive oxygen species (ROS) play an important role as a signaling molecule in the control of vascular tone and endothelial function. Increased ROS bioavailability is associated with important processes underlying vascular injury in cardiovascular disease such as endothelial dysfunction, vascular remodeling, and inflammation. Studies focusing on molecular mechanisms showed a link between overproduction of ROS in the vasculature and ethanol-induced hypertension. Of the ROS generated in vascular cells, superoxide anion (O2(-)) and hydrogen peroxide (H2O2) appear to be especially important. Ethanol-mediated generation of O2(-) and H2O2 in vascular tissues is associated with elevations in intracellular calcium ([Ca(2+)]i), reduced nitric oxide (NO) bioavailability, endothelial dysfunction and vasoconstriction. O2(-) can also act as a vascular signaling molecule regulating signaling pathways that lead to vascular contraction. Thus, through increased generation of ROS and activation of redox-sensitive pathways, ethanol induces vascular dysfunction, a response that might contribute to the hypertension associated with ethanol consumption. The present article reviews the role of ROS in vascular (patho)biology of ethanol.

Consequence of hyperhomocysteinaemia on α1-adrenoceptor-mediated contraction in the rat corpus cavernosum: the role of reactive oxygen species

Our main objective was to investigate the mechanisms underlying the effects of hyperhomocysteinaemia (HHcy) on contractile response mediated by α1‐adrenoceptors in the rat corpus cavernosum.

Antidepressivos: uso, adesão e conhecimento entre estudantes de medicina

This study assessed the degree of adherence and drug-related awareness and opinions regarding the importance of guidance with respect to treatment among medical students who use antidepressants. It is a cross-sectional descriptive study, carried out in a public Medical School in the state of Sao Paulo, Brazil. Of the 289 students interviewed, 33 (11.4%) use or had already used antidepressants, with fluoxetine being the most prescribed. The nurse was not cited as being responsible for guidance on the antidepressant. Although most students had received guidance on antidepressants, they did not heed guidance and still had doubts regarding their use. There was a statistically significant association regarding the consumption of other drugs in addition to antidepressants and the existence of side effects, as well as regarding an increase of the dosage without medical consultation and the existence of such side effects. Actions are necessary to acknowledge the importance of the teaching of psychopharmacology in the training of the medical professional and for greater harmony between theory and practice.

Quality of life and depressive symptoms in Parkinson's disease.

we have recently used the 39-item Parkinson’s Disease Questionnaire (PDQ-39) and its eight dimensions and the 15-item GDS (GDS-15) to assess quality of life and depressive symptoms in PD patients, respectively. We divided the patients into two groups (PD without depression and PD with depression) according to the GDS-15 cutoff score of eight proposed for the screening of depression in PD.

Adherence to medication among patients with Parkinson's disease treated at a specialized outpatient unit

Parkinsons disease is universal and the second most prevalent neurodegenerative disease among the elderly affecting between 0.5 and 1% of the population between 65 and 69 years of age. Adherence to medication is considered the main determinant for the effectiveness of treatment, but only recently has it been studied in patients with Parkinsons disease. This cross-sectional and descriptive study assessed adherence to medication in 112 patients with Parkinsons disease who regularly attended the movement disorder outpatient unit at the Hospital das Clinicas of the School of Medicine of Ribeirao Preto, University of São Paulo, using the Morisky and Green test and an instrument that assesses attitudes of medicine intake (IAAFTR). Of the patients interviewed, 53% failed to adhere to treatment and 52% did not take the medication at the correct time. Patients should receive guidance about the importance of taking their medication at the correct time, understanding the benefits that adherence to medication can provide. They should also be aware that doses not taken, taken in excess or not taken at the prescribed times can reduce their response to treatment, having a negative effect on the clinical outcome and quality of life, thereby generating higher costs to public health in the country.

Adesão à medicação em pacientes com doença de Parkinson atendidos em ambulatório especializado

A doenca de Parkinson e universal, sendo a segunda doenca neurodegenerativa mais comum em idosos e tem alta prevalencia, afetando entre 0,5 e 1% da populacao com idade entre 65 e 69 anos. A adesao a terapia medicamentosa e considerada o principal determinante para a efetividade do tratamento, porem apenas recentemente vem sendo estudado em pacientes com doenca de Parkinson. Trata-se de estudo transversal e descritivo que avaliou a adesao a terapia com levodopa em 112 pacientes com doenca de Parkinson que frequentavam regularmente o ambulatorio de disturbios do movimento do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo utilizando o teste Morisky e Green e o instrumento que avalia atitudes frente a tomada dos remedios (IAAFTR). Dos pacientes entrevistados, 53% nao apresentaram adesao ao tratamento e 52% nao tomam a medicacao no horario correto. Os pacientes devem ser orientados sobre a importância de ingerir sua medicacao no horario correto, entendendo os beneficios que a adesao pode proporcionar estando cientes de que doses nao tomadas, tomadas em excesso, ou em horarios diferentes dos prescritos podem diminuir sua resposta ao tratamento, afetando negativamente sua evolucao clinica e qualidade de vida, gerando maiores custos a saude publica do pais.Pesquisas sobre saude geral tem relacionado coesao familiar a fatores socioeconomicos e comportamentais. O objetivo deste estudo foi investigar a associacao entre coesao familiar e fatores socioeconomicos, comportamentais e de saude bucal. Este foi um estudo transversal com amostra por conglomerados em dois estagios. A amostra randomizada de 524 adolescentes era proveniente de escolas publicas da cidade de Piracicaba-SP. As variaveis foram avaliadas por questionarios autoaplicaveis e os dados de saude bucal, pelos indices CPO e CPI. A coesao familiar percebida pelo adolescente foi avaliada por meio da escala de adaptabilidade e coesao familiar. Analise univariada e regressao logistica multinominal mostraram que adolescentes com baixa coesao familiar apresentaram mais chance de terem baixa renda (OR 2,28 IC95% 1,14-4,55), presenca de carie (OR 2,23 IC95% 1,21-4,09) e baixa frequencia de escovacao diaria (OR 1,91 IC95% 1,03-3,54). Adolescentes com alta coesao familiar apresentaram mais chance que adolescentes com media coesao de terem alta renda e fator de protecao contra o habito de tabagismo. Desta forma, a coesao familiar percebida pelo adolescente associou-se com variaveis comportamentais, socioeconomicas e de saude bucal, indicando a importância de uma abordagem integral da saude do paciente.Overall health surveys have related family cohesion to socio-economic status and behavioral factors. The scope of this study was to investigate the association between family cohesion and socio-economic, behavioral and oral health factors. This was a, cross-sectional study with two-stage cluster sampling. The random sample consisted of 524 adolescents attending public schools in the city of Piracicaba-SP. Variables were evaluated by self-applied questionnaires and caries and periodontal disease were assessed by DMF-T and CPI indices. The adolescents perception of family cohesion was assessed using the family adaptability and cohesion scale. Univariate and multinomial logistic regression shows that adolescents with low family cohesion were more likely than those with medium family cohesion to have low income (OR 2,28 95% CI 1,14- 4,55), presence of caries (OR 2,23 95% CI 1,21-4,09), less than two daily brushings (OR 1,91 95% CI 1,03-3,54). Adolescents with high family cohesion were more likely than those with medium family cohesion to have high income and protective behavior against the habit of smoking. Thus, the data shows that adolescent perception of family cohesion was associated with behavioral, socio-economic and oral health variables, indicating the importance of an integral approach to patient health.

Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species

To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.