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Editorial

Alterations Resulting From Exposure to Mercury in Normotensive and Hypertensive Rats

Luana Urbano Pagan et al. Marcelo Diarcadia Mariano Cezar Ricardo Luiz Damatto

Mercury is a chemical element still widely used in industrial processes and present in many appliances used daily by the population. However, mercury can be extremely toxic to our body and lead to the development of several diseases such as blindness, deafness, intellectual disability, paralysis, cancer, renal dysfunction, and it can also induce cardiac alterations.^,

Studies have shown that exposure to mercury can cause changes in the cardiovascular system, such as systemic arterial hypertension, coronary dysfunction, cardiac arrhythmia, and increase the risk of myocardial infarction.^, In humans, high blood mercury levels were correlated with increased systolic and diastolic blood pressure.

[…]

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Original Article

Effects of Chronic Exposure to Mercury on Angiotensin-Converting Enzyme Activity and Oxidative Stress in Normotensive and Hypertensive Rats

Dalton Valentim Vassallo et al. Maylla Ronacher Simões Karina Giuberti Bruna Fernandes Azevedo … Rogerio Faustino Ribeiro Junior Mercedes Salaices Ivanita Stefanon

Abstract

Background:

Mercury’s deleterious effects are associated with increased cardiovascular risk.

Objective:

To determine whether chronic exposure to inorganic mercury increases the activity of angiotensin-converting enzyme and its relationship with oxidative stress in several organs and tissues.

Methods:

We studied male Wistar and spontaneously hypertensive rats (SHR) (3-month-old) exposed or not to HgCl₂ for 30 days. At the end of treatment, we investigated the following: changes in body weight, hemodynamic parameters, angiotensin-converting enzyme (ACE) activity and oxidative stress in the heart, aorta, lung, brain and kidney in hypertensive compared to normotensive animals. A value of p < 0.05 was considered significant.

Results:

Chronic exposure to HgCl₂ did not affect weight gain in either group. Systolic blood pressure, measured weekly, did not increase in Wistar rats but showed a small increase in SHR rats. We also observed increases in left ventricular end-diastolic pressure and ACE activity in the plasma and hearts of normotensive rats. In the SHR+Hg group, ACE activity increased in plasma but decreased in kidney, lung, heart, brain and aorta. Oxidative stress was assessed indirectly by malondialdehyde (MDA) production, which increased in Hg-treated rats in both plasma and heart. In the SHR+Hg group, MDA increased in heart and aorta and decreased in lungs and brain.

Conclusion:

These results suggest that chronic exposure to inorganic mercury aggravates hypertension and produces more expressive changes in ACE activity and oxidative stress in SHRs. Such exposure affects the cardiovascular system, representing a risk factor for the development of cardiovascular disorders in normotensive rats and worsening of pre-existing risks for hypertension.

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Original Article

Pericardial Parietal Mesothelial Cells: Source of the Angiotensin-Converting-Enzyme of the Bovine Pericardial Fluid

Ilsione Ribeiro de Sousa Filho et al. Isabela Cabral Cavicchioli Pereira Lourimar José de Morais Livia das Graças Vieito Lombardi Teodoro … Maria Laura Pinto Rodrigues Roseli Aparecida da Silva Gomes

Abstract

Background:

Angiotensin II (Ang II), the primary effector hormone of the renin-angiotensin system (RAS), acts systemically or locally, being produced by the action of angiotensin-converting-enzyme (ACE) on angiotensin I. Although several tissue RASs, such as cardiac RAS, have been described, little is known about the presence of an RAS in the pericardial fluid and its possible sources. Locally produced Ang II has paracrine and autocrine effects, inducing left ventricular hypertrophy, fibrosis, heart failure and cardiac dysfunction. Because of the difficulties inherent in human pericardial fluid collection, appropriate experimental models are useful to obtain data regarding the characteristics of the pericardial fluid and surrounding tissues.

Objectives:

To evidence the presence of constituents of the Ang II production paths in bovine pericardial fluid and parietal pericardium.

Methods:

Albumin-free crude extracts of bovine pericardial fluid, immunoprecipitated with anti-ACE antibody, were submitted to electrophoresis (SDS-PAGE) and gels stained with coomassie blue. Duplicates of gels were probed with anti-ACE antibody. In the pericardial membranes, ACE was detected by use of immunofluorescence.

Results:

Immunodetection on nitrocellulose membranes showed a 146-KDa ACE isoform in the bovine pericardial fluid. On the pericardial membrane sections, ACE was immunolocalized in the mesothelial layer.

Conclusions:

The ACE isoform in the bovine pericardial fluid and parietal pericardium should account at least partially for the production of Ang II in the pericardial space, and should be considered when assessing the cardiac RAS.

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Original Article

Hierarchical Analysis of Hypertension with the Polymorphic Variant of the ACE Gene and Other Risk Factors in the Elderly

Breno Barreto Ribeiro et al. Pedro Eleutério dos Santos Neto Jairo Evangelista Nascimento João Marcus Oliveira Andrade … Alanna Fernandes Paraíso Sérgio Henrique Sousa Santos Marise Fagundes Silveira Andréa Maria Eleutério de Barros Lima Martins

Abstract

Background:

Hypertension is a clinical condition of multifactorial etiology that imposes serious harm to the health of elderly individuals. Despite the fact that cardiovascular disorders influence the development of hypertension in this age group, several other genetic and environmental factors have been described in the literature, including the polymorphic variant of the angiotensin-converting enzyme (ACE) gene and the distribution of body fat.

Objective:

To assess the prevalence of hypertension among elderly individuals and its possible correlation with the I/D polymorphic variant of the ACE gene and other associated risk factors.

Methods:

Population-based study using a hierarchical model and including 387 elderly individuals residing in the urban area of Ibiaí (Minas Gerais, Brazil).

Results:

On statistical analysis, the polymorphic variant of the ACE gene was not associated with hypertension (p = 0.316). On the other hand, there was a significant association between hypertension and the variables female sex, absence of a partner, consumption of more than one portion of salt per day, and changes in body mass index and waist-to-hip ratio.

Conclusion:

Although the polymorphic variant of the ACE gene showed no influence on the prevalence of hypertension in elderly individuals, some variables such as individual, socioeconomic, metabolic, and behavioral habits were associated with this condition.

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Letter to the Editor

ACE I/D Gene Polymorphism in Children with Family History of Premature Coronary Disease

Dilek Yý lmaz Çiftdoð an

Additional information:

In addition to ACE I/D gene polymorphism, glycoprotein IIIa, factor V G1691A, factor V H1299R, prothrombin G20210A and apolipoprotein E polymorphism had been investigated in the same study group. These results were published in various journals.

* Ciftdoğan DY. Glycoprotein IIIa gene polymorphism in children with a family history of premature coronary artery disease. Acta Cardiol. 2010 Dec;65(6):695; author reply 695-6.

[…]

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Original Article

Survival and Predictive Factors of Lethality in Hemodyalisis: D/I Polymorphism of The Angiotensin I-Converting Enzyme and of the Angiotensinogen M235T Genes

Mauro Alves et al. Nelson Albuquerque de Souza e Silva Lucia Helena Alvares Salis Basilio de Bragança Pereira … Paulo Henrique Godoy Emília Matos do Nascimento Jose Mario Franco Oliveira

Background:

End-stage kidney disease patients continue to have markedly increased cardiovascular disease morbidity and mortality. Analysis of genetic factors connected with the renin-angiotensin system that influences the survival of the patients with end-stage kidney disease supports the ongoing search for improved outcomes.

Objective:

To assess survival and its association with the polymorphism of renin-angiotensin system genes: angiotensin I-converting enzyme insertion/deletion and angiotensinogen M235T in patients undergoing hemodialysis.

Methods:

Our study was designed to examine the role of renin-angiotensin system genes. It was an observational study. We analyzed 473 chronic hemodialysis patients in four dialysis units in the state of Rio de Janeiro. Survival rates were calculated by the Kaplan-Meier method and the differences between the curves were evaluated by Tarone-Ware, Peto-Prentice, and log rank tests. We also used logistic regression analysis and the multinomial model. A p value ≤ 0.05 was considered to be statistically significant. The local medical ethics committee gave their approval to this study.

Results:

The mean age of patients was 45.8 years old. The overall survival rate was 48% at 11 years. The major causes of death were cardiovascular diseases (34%) and infections (15%). Logistic regression analysis found statistical significance for the following variables: age (p = 0.000038), TT angiotensinogen (p = 0.08261), and family income greater than five times the minimum wage (p = 0.03089), the latter being a protective factor.

Conclusions:

The survival of hemodialysis patients is likely to be influenced by the TT of the angiotensinogen M235T gene.

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Letter to the Editor

Angiotensin-converting Enzyme Genetic Polymorphism

Somsri Wiwanitkit et al. Viroj Wiwanitkit

Sir Editor,

The recent report on “angiotensin-converting enzyme (ACE) genetic polymorphism.” is very interesting. Albuquerque et al. concluded that “the DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with best echocardiographic profile.” In fact, the polymorphism of ACE is different in different countries and the relationship to clinical disorder is widely mentioned. The study of ACE polymorphism has proved to be useful in management of cardiac patients, especially for selection of proper cardiac drug. However, the relationship to cardiac pathology is still controversial. Similar to the present study, the ventricular function abnormality determined by EKG was proposed for interrelationship with ACE polymorphism by Yu Jin et al. Nevertheless, the small sample size in the published studies^, is the main obstacle for conclusions. The effect of race in clinical relationship of ACE polymorphism requires a very large study in order to lead to conclusions.

[…]

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Artigo Original

ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

Renato De Vecchis et al. Giuseppina Di Biase Carmelina Ariano Carmela Cioppa … Anna Giasi Antonio Ciccarelli Armando Pucciarelli Salvatore Cantatrione

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF – whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors “high” dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

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Artigo Original

Gender differences in serum angiotensin-converting enzyme activity and blood pressure in children: an observational study

Patricia Landazuri et al. Claudia Granobles Nelsy Loango

BACKGROUND: Angiotensin-converting enzyme (ACE) is a key enzyme of the renin-angiotensin system that plays an important role in regulating blood pressure. ACE enzyme activity and its relationships with blood pressure (BP) during childhood and adolescence have not yet been clearly established. OBJECTIVE: To determine serum ACE (S-ACE) levels and BP changes in school children between 8 and 18 years of age and how S-ACE and BP in males and females might differ, as well as to determine S-ACE and BP relationships. METHODS: Blood pressure, height, weight, body mass index (BMI), and S-ACE were measured in 501 children. RESULT: Mean S-ACE values were higher in boys (143.7±57.1) than in girls (130.2 ± 54.9) (p = 0.004). S-ACE values decreased in girls and increased in boys with age, and values for girls were lower than for age-matched boys after onset of puberty. Age was a strong determinant of BP levels in both genders. We found a relationship between ACE and systolic blood pressure (SBP) and diastolic blood pressure (DBP) in girls (SBP r= -0.20 p<0.001 DBP r=0.12 p<0.03). BMI had greater correlation with SBP and DBP in girls (r=0.37, and 0.31, respectively; p < 0.001) than in boys (r=0.26, and 0.25 respectively; p<0.001). CONCLUSION: These results indicate that gender differences in serum ACE activity exist in the children from this study. This activity was lower and decreased with age in girls, while BP increased. Because sexual dimorphism in BP emerges in puberty, our findings suggest that gonadal hormones might affect S-ACE activity and BP. These results may have important therapeutic implications.

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