Chronic and acute effects of kefir: the role of angiotensin converting enzyme inhibition instead of nitric oxide balance

Probiotic consumption promotes numerous health benefits. The aim of this study is 1) to evaluate the antihypertensive effect of kefir in a hypertension rat model caused by the administration of the nitric oxide synthesis inhibitor, L-NAME, and 2) to evaluate the acute angiotensin converting enzyme (ACE) inhibitory activity of the soluble nonbacterial fraction (SNBF) of kefir. To develop the first aim, male rats were separated into three groups: control group (C) treated with 0.3 mL/100 g of milk; L-NAME group (LN) received 10 mg/kg of said inhibitor; and Kefir group (K) treated with 0.3 mL/100 g of kefir plus L-NAME (10 mg/kg of said inhibitor). The treatments were given by oral gavage twice a day for four weeks. For the second aim"instead additionally, male rats received angiotensin I (in bolus) in three doses (Ang I: 0.03, 3 and 300 µg/kg) and were separated into two groups: a) received captopril (30 mg/kg i.v.) and b)received SNBF of kefir (5 mL/kg i.v.). Blood pressure were evaluated before and after Ang I. After treatment, hemodynamic parameters were evaluated, heart weight was recorded, and body weight gain was calculated. SNBF of kefir did not decrease the blood pressure for L-NAMEtreated animals, and no changes were observed in the cardiac parameters. However, the SNBF of kefir demonstrated acute inhibition of ACE in vivo similar to that of captopril. Thus, our results suggest that kefir may improve human cardiovascular systems by using mechanisms independent of nitric oxide syntheses. Additionally, the renin angiotensin system is probably the most important system involved in kefir effect regarding hypertension.

Vascular Transcriptome Profiling Reveals Aging-Related Genes in Angiotensin Ⅱ-Induced Hypertensive Mouse Aortas / 中国医学科学杂志(英文版)

Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.

Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea andcreatinine variations in patients with dementia due to Alzheimer disease / Efectos farmacogenéticos de inhibidores de la enzima convertidora de la angiotensina en variaciones de urea y creatinina asociadas con el envejecimiento en pacientes con demencia de la enfermedad de Alzheimer

Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding geneticallymediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations. Results: For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3.074 mg/ dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis. Conclusions: Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Antecedentes: El deterioro de la función renal depende de la edad y los factores vasculares. La literatura sobre los efectos de fármacos antihipertensivos mediada genéticamente en la función renal es pobre. Objetivo: Estimar las variaciones de urea y creatinina a través del análisis farmacogenético de los efectos antihipertensivos de los inhibidores de la enzima convertidora de angiotensina (iECA) en pacientes con demencia debido a la enfermedad de Alzhaimer. Métodos: Fueron reclutados pacientes consecutivos mayores de 60 años de edad con enfermedad de Alzheimer y sin antecedentes de trasplante renal o diálisis. Se determinaron correlaciones prospectivas durante un año entre los cambios en los niveles sanguíneos de urea y creatinina, considerando genotipos y haplotipos de ACE (rs1800764 y rs4291) y el tratamiento con iECA a y las variaciones en la presión arterial. Resultados: De 190 pacientes, 152 presenaron hipertensión, 122 usaron iECA. Las frecuencias de alelos polimórficos fueron de 0.492 para rs1800764-C y 0.337 para rs4291-T, los dos alelos en equilibrio de Hardy-Weinberg. No se determinaron fluctuaciones anuales significativas en los niveles de urea o creatinina, pero sus variaciones concomitantes se asociaron fuertemente (ρ= <0.0001). Cada alelo A de rs4291 condujo a aumentos anuales de 3.074 mg/dL en urea y 0.044 mg/dL en creatinina, mientras que el uso de iECA fue protector para las variaciones en la creatinina. El uso de iECA también fue protector para las personas con rs1800764-CT/rs4291-AA, mientras que los portadores de rs1800764-CT/rs4291-AT tuvieron reducciones de creatinina más altas, particularmente cuando se usó iECA. Conclusión: Los efectos de iECA en la variación de la creatinina son genéticamente mediadas e independiente de las variaciones en la presión arterial en pacientes de edad avanzada con la enfermedad de Alzheimer.

The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

PURPOSE: Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). MATERIALS AND METHODS: We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. RESULTS: Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cho-lesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. CONCLUSION: Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD.

A Polymorphism of the Renin Gene rs6682082 Is Associated with Essential Hypertension Risk and Blood Pressure Levels in Korean Women

PURPOSE: The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans. MATERIALS AND METHODS: To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects. RESULTS: Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4+/-0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant. CONCLUSION: We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.

Gender Differences in the Association between Serum gamma-Glutamyltransferase and Blood Pressure Change: A Prospective Community-Based Cohort Study

We evaluated the gender differences in the relation of baseline serum gamma-glutamyltransferase (GGT) levels to blood pressure (BP) change during 4 yr. 4,025 normotensive subjects (1,945 men and 2,080 women) who aged 40-69 yr at baseline participated in the Ansung-Ansan cohort of the Korean Genome Epidemiology Study were included. The associations of GGT with baseline BP or 4-yr change of BP were evaluated. GGT levels were associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline after adjusting for age, body mass index (BMI), HDL-cholesterol, triglyceride, C-reactive protein (CRP), current smoking status and alcohol intake (SBP, beta=1.28, P<0.001; DBP, beta=1.41, P<0.001). GGT levels were also associated with 4-yr change in BP after adjusting for age, BMI, HDL-cholesterol, triglyceride, CRP, current smoking status, alcohol intake and SBP (SBP, beta=1.08, P=0.001; DBP, beta=0.64, P=0.003). This association was statistically significant in men (SBP, beta=1.82, P<0.001; DBP, beta=1.05, P=0.001), but not in women (SBP, beta=0.38, P=0.466; DBP, beta=-0.37, P=0.304). Remarkably, this association between GGT and BP was significant in men at 40-49 yr of age. In summary, we found positive associations between GGT levels at baseline and the change of BP. The relation of GGT level and the change of BP was only significant in men, not in women, which warrants further studies to elucidate the biologic mechanisms.

Asociación y efectos de interacción en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en la población antioqueña / Association and interaction of AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R and PTGS2 genes on the risk of hypertension in Antioquian population

Introducción. La hipertensión arterial es una enfermedad multifactorial influenciada por componentes genéticos y ambientales, cuya prevalencia varía entre grupos étnicos. Se han llevado a cabo numerosos estudios en genes de sistemas reguladores de la presión arterial, como el sistema renina-angiotensinaaldosterona, el sistema nervioso simpático, los factores endoteliales, y el balance de sodio, mostrando resultados incongruentes entre poblaciones. Objetivos. Evaluar el efecto de variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 y del componente ancestral individual, sobre la hipertensión arterial y las cifras de presión arterial en una muestra de población antioqueña. Materiales y métodos. Se genotipificaron 107 casos y 253 controles para 12 variantes en los genes AGT , AGTR1 , ACE , ADRB2 , DRD1 , ADD1 , ADD2 , ATP2B1 , TBXA2R y PTGS2 , y para 20 marcadores informativos de ascendencia. Se evaluó la asociación de los polimorfismos y sus interacciones, y de la composición genética ancestral con hipertensión y cifras de presión arterial. Resultados. Los genes ADD2 , rs4852706 (OR=3,0; p=0,023); DRD1 , rs686 (OR=0,38; p=0,012) y ADRB2 , rs1042718 (OR=10,0; p=0,008); y combinaciones genotípicas de DRD1 con AGTR1 ; de AGT con ADD1 ; y de ADD1 con ATP2B1 y PTGS2 , se asociaron con hipertensión arterial. El componente ancestral amerindio se asoció con disminución en la presión arterial diastólica. Conclusiones. Variantes en los genes ADD2 , DRD1 , ADRB2 , AGTR1 , AGT , ADD1 , ATP2B1 y PTGS2 , individualmente o en su interacción, se encuentran asociadas con hipertensión. El componente ancestral amerindio tiene un efecto sobre las cifras de presión arterial.

Introduction: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. Objectives: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. Methods and materials: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Results: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Conclusion: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

OBJECTIVE: The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension. METHODS: A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies. RESULTS: The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively). CONCLUSIONS: The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension. .

Exaggerated blood pressure response during the exercise treadmill test as a risk factor for hypertension

Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) has been considered to be a risk factor for hypertension. The relationship of polymorphisms of the renin-angiotensin system gene with hypertension has not been established. Our objective was to evaluate whether EBPR during exercise is a clinical marker for hypertension. The study concerned a historical cohort of normotensive individuals. The exposed individuals were those who presented EBPR. At the end of the observation period (41.7 months = 3.5 years), the development of hypertension was analyzed within the two groups. Genetic polymorphisms and blood pressure behavior were assessed as independent variables, together with the classical risk factors for hypertension. The I/D gene polymorphism of the angiotensin-converting enzyme and M235T of angiotensinogen were ruled out as risk factors for hypertension. EBPR during ETT is not an independent influence on the chances of developing hypertension. No differences were observed between the hypertensive and normotensive individuals regarding gender (P = 0.655), skin color (P = 0.636), family history of hypertension (P = 0.225), diabetes mellitus (P = 0.285), or hypertriglyceridemia (P = 0.734). The risk of developing hypertension increased with increasing body mass index (BMI) and advancing age. The risk factors, which independently influenced the development of hypertension, were age and BMI. EBPR did not constitute an independent risk factor for hypertension and is probably a preclinical phase in the spectrum of normotension and hypertension.

Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h²), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h² = 0.37 ± 0.10, P < 0.05; diastolic BP: h² = 0.39 ± 0.09, P < 0.05; TPA: h² = 0.24 ± 0.09, P < 0.05). Significant genetic (r g) and environmental (r e) correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

Physical characteristics at different ages / Características físicas en diferentes edades

The purpose of this study was to study, observe, and clarify the dynamics of physical growth, as well as changes of some morphometrical and physiological variables of Kosovo population. 17,894 males from Kosovo between 6 and 51 years of age and older, were measured: body height, body weight, BMI, systolic pressure, diastolic pressure, heart rate, and VO max were recorded. The measurement data were processed through these descriptive statistical parameters: Mean, Standard-Deviation and the Coefficient of Variation, SD shows the similar dispersion of results between one age and another. CV signifies the reliability of the measurements that were carried out. The curve of body height for individuals between 6 and 17 years of age shows increases, for individuals between 18 and 40 years of age shows stable values, while for indiividuals above 40 years of age indicate a decrease.Body height difference between adults shows that adultsbetween 18 and 30 years old have the higher body height values, compared with the other two groups of tested adults. Body weight for individualsbetween 6 and 50 years old shows consistent increase of value. In individuals above 51 years of age, body weight decreases rapidly. According to BMIvalues individuals between 6 and 13 years of age were underweight. Those between 14 and 35 years of age, as well as those above 51 years of age showed normal weight. On the other hand, those between 36 and 50 years of age were slightly overweight. Systolic and diastolic blood pressure values were higher as age increased, however were not above normal values. The best results of HR and VO2max were reported in adults between 19 and 27 years of age.

El objetivo de este trabajo fue estudiar, observar, y para aclarar la dinámica de crecimiento físico, así como los cambios de algunas variables morfométricas y fisiológicas de la población de Kosovo. En 17.894 hombres en Kosovo, de entre 6 y 51 años, se tomaron las siguientes medidas: Altura y peso corporal, IMC, presiones sistólica y diastólica, frecuencia cardíaca, VO2 máx. Los datos fueron procesados a través de los siguientes parámetros estadísticos descriptivos: media, desviación estándar y coeficiente de variación. La DS muestra la dispersión de los resultados de acuerdo a la edad. CV determina la fiabilidad de las mediciones que se hicieron. La curva de la altura del cuerpo entre 6-17 años de edad aumentó entre los 18 y 40 años de edad, mientras que para individuos de más de 40 años la curva disminuye. La altura corporal mostró que los adultos entre 18-30 años son más altos, en comparación con otros dos grupos. El peso corporal aumenta desde los 6 a los 50 años edad, mientras que después de los 51 años se produce rápidamente su disminución. De acuerdo a los valores de IMC, los individuos entre 6-13 años de edad presentaban bajo peso. Los individuos entre 14-35 años y superiores a 51 años presentaban un peso normal. Los individuos entre 36-50 años, presentaron un ligero sobrepeso. Aumentaron las presiones sistólica y diastólica de acuerdo a la edad, pero no por encima del valor normal. Los mejores resultados de la frecuencia cardiaca y VO2máx se alcanzaron en los adultos entre 19 y 27 años.

Efeito do exercício físico e do polimorfismo T-786C na pressão arterial e no fluxo sanguíneo de idosas / Effect of physical activity and t-786C polymorphism in blood pressure and blood flow in the elderly / Efecto del ejercicio físico y del polimorfismo T-786C en la presión arterial y en el flujo sanguíneo de añosas

FUNDAMENTO: O polimorfismo T-786C do gene da sintetase do óxido nítrico endotelial (eNOS) e a produção de ânion superóxido podem diminuir a produção e biodisponibilidade do óxido nítrico, comprometendo o grau de vasodilatação, podendo este efeito ser revertido pelo exercício físico. OBJETIVO: Investigar a influência do treinamento aeróbico e do polimorfismo T-786C nas concentrações dos metabólitos do óxido nítrico (NOx), no fluxo sanguíneo (FS) e na pressão arterial (PA). MÉTODOS: Trinta e duas idosas pré-hipertensas (59 ± 6 anos) foram separadas em dois grupos de acordo com o polimorfismo T-786C (TT e TC+CC). Foram analisadas as concentrações de NOx (plasma) e fluxo sanguíneo por pletismografia de oclusão venosa em repouso, 1, 2 e 3 minutos pós-oclusão (FS-0, FS-1, FS-2, FS-3, respectivamente). As avaliações foram realizadas antes e após 6 meses de um programa de exercício aeróbico. RESULTADOS: Nas avaliações pré-treinamento, os níveis de NOx foram menores no grupo TC+CC em relação ao grupo TT. O grupo TT apresentou correlações entre NOx e FS-0 (r = 0,6) e pressão arterial diastólica (PAD) e FS-0 (r = -0,7), porém nenhuma correlação foi encontrada no grupo TC+CC. Nas avaliações pós-treinamento, ocorreram correlações entre NOx e FS-0 (r = 0,6) e nas mudanças do NOx e PAD (r = -0,6) no grupo TT. Também foram obtidas correlações entre PAD e FS-1 (r = -0,8), PAD e FS-2 (r = -0,6), PAD e FS-3 (r = -0,6), nas mudanças entre NOx e FS-1 (r = 0,8) e mudanças do NOx e PAD (r = -0,7) no grupo TC+CC. CONCLUSÃO: Conclui-se que 6 meses de exercício aeróbico podem contribuir para aumentar as relações existentes entre NO, PA e FS em idosas portadores do alelo C.

BACKGROUND: The T-786C polymorphism of the gene for endothelial nitric oxide synthase (eNOS) and superoxide anion production may reduce production and bioavailability of nitric oxide, affecting the degree of vasodilation. This effect can be reversed by exercise. OBJECTIVE: To investigate the influence of aerobic training and T-786C polymorphism in the concentrations of nitric oxide metabolites (NOx) in blood flow (BF) and blood pressure (BP). METHODS: Thirty-two elderly pre-hypertensive women (59 ± 6 years old) were divided into two groups according to the T-786C polymorphism (TT and TC + CC). We analyzed the concentrations of NOx (plasma) and blood flow by venous occlusion plethysmography at rest, 1, 2 and 3 minutes post-occlusion (BF-0, BF-1 BF-2 BF-3, respectively). Evaluations were performed before and after 6 months of a program of aerobic exercise. RESULTS: In the pre-training evaluations, NOx levels were lower in TC + CC group than in TT group. The TT group showed correlations between NOx and BF-0 (r = 0.6) and diastolic blood pressure (DBP) and BF-0 (r = -0.7), but no correlation was found in TC + CC group. In the post-training evaluations, there were correlations between NOx and BF-0 (r = 0.6) and the changes in NOx and DBP (r = -0.6) in TT group. There were also correlations between DBP and BF-1 (r = -0.8), DBP, and BF-2 (r = -0.6), DBP, and BF-3 (r = -0.6), in the changes between NOx and BF-1 (r = 0.8) and changes in NOx and DBP (r = -0.7) in TC + CC group. CONCLUSION: It was concluded that 6 months of aerobic exercise can increase the relationship between NO, BP and BF in elderly of allele C carriers.

FUNDAMENTO: El polimorfismo T-786C del gen de la sintetasa del óxido nítrico endotelial (eNOS) y la producción de anión superóxido pueden disminuir la producción y biodisponibilidad del óxido nítrico, comprometiendo el grado de vasodilatación, pudiendo este efecto ser revertido por el ejercicio físico. OBJETIVO: Investigar la influencia del entrenamiento aeróbico y del polimorfismo T-786C en las concentraciones de los metabolitos del óxido nítrico (NOx), en el flujo sanguíneo (FS) y en la presión arterial (PA). MÉTODOS: Treinta y dos añosas prehipertensas (59 ± 6 años) fueron separadas en dos grupos de acuerdo con el polimorfismo T-786C (TT y TC+CC). Fueron analizadas las concentraciones de NOx (plasma) y flujo sanguíneo por pletismografía de oclusión venosa en reposo, 1, 2 y 3 minutos post oclusión (FS-0, FS-1, FS-2, FS-3, respectivamente). Las evaluaciones fueron realizadas antes y después de 6 meses de un programa de ejercicio aeróbico. RESULTADOS: En las evaluaciones pre entrenamiento, los niveles de NOx fueron menores en el grupo TC+CC en relación al grupo TT. El grupo TT presentó correlaciones entre NOx y FS-0 (r = 0,6) y presión arterial diastólica (PAD) y FS-0 (r = -0,7), sin embargo ninguna correlación fue encontrada en el grupo TC+CC. En las evaluaciones post entrenamiento, ocurrieron correlaciones entre NOx y FS-0 (r = 0,6) y en los cambios del NOx y PAD (r = -0,6) en el grupo TT. También fueron obtenidas correlaciones entre PAD y FS-1 (r = -0,8), PAD y FS-2 (r = -0,6), PAD y FS-3 (r = -0,6), en los cambios entre NOx y FS-1 (r = 0,8) y cambios del NOx y PAD (r = -0,7) en el grupo TC+CC. CONCLUSIÓN: Se concluye que 6 meses de ejercicio aeróbico pueden contribuir a aumentar las relaciones existentes entre NO, PA y FS en añosas portadoras del alelo C.

Fatores genéticos na agregação familiar da pressão arterial de famílias nucleares portuguesas / Genetic factors in familial aggregation of blood pressure of portuguese nuclear families / Factores genéticos en la agregación familiar de la presión arterial de familias nucleares portuguesas

FUNDAMENTO: Apesar da elevada prevalência de hipertensão arterial em Portugal, a importância relativa que os genes possam exercer na manifestação final dos valores da pressão arterial (PA) parece pouco estudada. OBJETIVOS: Verificar a presença, indireta, de transmissão vertical de fatores genéticos entre progenitores e descendentes nos valores da PA, e estimar a contribuição dos fatores genéticos responsáveis pela variação dos valores de PA em termos populacionais. MÉTODOS: A amostra foi constituída por 367 indivíduos (164 progenitores e 203 descendentes) pertencentes a 107 famílias nucleares provenientes de diferentes regiões do norte de Portugal, participantes do projeto "Famílias Activas". A PA foi medida com um aparelho digital da marca Omron®, modelo M6 (HEM-7001-E). Foram utilizados os softwares estatísticos SPSS 15.0 para a análise exploratória de dados e o cálculo das estatísticas descritivas, e o PEDSTATS para analisar o comportamento genérico das variáveis entre os diferentes membros da família. O cálculo das correlações entre familiares e as estimativas de heritabilidade foram realizados nos módulos FCOR e ASSOC do software de epidemiologia genética S.A.G.E., versão 5.3. RESULTADOS: Para a PA sistólica (PAS), os valores das correlações entre os graus de parentesco foram de baixos a moderados (0,21< r <0,35). Para a PA diastólica (PAD), os valores encontrados foram moderados (0,24< r <0,50). Os fatores genéticos explicaram cerca de 43 e 49% da variação total da PAS e da PAD, respectivamente. CONCLUSÃO: Os resultados evidenciaram que uma quantidade moderada da PAS e da PAD é imputada a fatores genéticos.

BACKGROUND: Despite of the increase in the prevalence of hypertension in Portugal, the importance of genetic factors in blood pressure (BP) has not been studied extensively in our country. OBJECTIVES: To verify the indirect presence of vertical transmission of genetic factors between parents and children in BP values, and to estimate the magnitude of genetic factors contributing for variation in BP values in the population. METHODS: Sample size comprises 367 individuals (164 parents and 203 children) pertaining the 107 nuclear families participating in "Familias Activas" project, proceeding from different regions of North Portugal. The BP was measured with Omron® model M6 (HEM-7001-E) digital device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the structure of each family data. Familial correlations and heritability estimates were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. RESULTS: For systolic BP (SBP), correlation values were low to moderate (0,21< r <0,35); for diastolic BP (DBP) values were found to be moderate (0,24< r <0,50). Genetic factors explain 43 and 49% of the total variation in SBP and DBP, respectively. CONCLUSION: A moderate amount of the SBP and the DBP is accounted for by genetic factors.

FUNDAMENTO: A pesar de la elevada prevalencia de hipertensión arterial en Portugal, la importancia relativa que los genes pueden ejercer en la manifestación final de los valores de la presión arterial (PA) nos parece poco estudiada. OBJETIVOS:Verificar la presencia, indirecta, de transmisión vertical de factores genéticos entre progenitores y descendientes en los valores de la PA, y estimar el aporte de los factores genéticos responsables de la variación de los valores de PA en términos poblacionales. MÉTODOS: La muestra estaba conformada por 367 individuos (164 progenitores y 203 descendientes) pertenecientes a 107 familias nucleares provenientes de diferentes regiones del norte de Portugal, participantes del proyecto "Familias Activas". La PA se midió con un aparato digital de la marca Omron®, modelo M6 (HEM-7001-E). Se utilizaron los softwares estadísticos SPSS 15.0 para el análisis exploratorio de datos y el cálculo de las estadísticas descriptivas, y el PEDSTATS para analizar el comportamiento genérico de las variables entre los diferentes miembros de la familia. El cálculo de las correlaciones entre familiares y las estimativas de heritabilidad se realizaron en los módulos FCOR y ASSOC del software de epidemiología genética S.A.G.E., versión 5.3. RESULTADOS: Para la PA sistólica (PAS), los valores de las correlaciones entre los grados de parentesco se mostraron bajos a moderados (0,21< r <0,35). Para la PA diastólica (PAD), los valores encontrados fueron moderados (0,24< r <0,50). Los factores genéticos explicaron cerca del 43 y el 49% de la variación total de la PAS y de la PAD, respectivamente. CONCLUSIÓN: Los resultados evidenciaron que se atribuye una cantidad moderada de la PAS y de la PAD a factores genéticos.

Perfil de presión arterial e historia familiar de hipertensión en niños escolares sanos de Santiago de Chile / Blood pressure and family history of hypertension in children from Santiago, Chile

Background: The prevalence of pediatric arterial hypertension (AHT) is approximately 1% to 2%. In the last ten years, mean blood pressure levels (BP) have raised due to obesity and changes in lifestyles. Family history (FH) of AHT is a risk factor to develop AHT inchildren. Aim: To assess blood pressure, cardiovascular risk factors and family history in healthy children of Santiago. Material and methods: Blood pressure, family history of AHT, birth weight(BW), gestational age, puberal stage, blood glucose, serum lipids and ultrasensitive Reactive C Protein (usCRP) were analyzed, using data from a study of early markers of atherosclerosis in children. Results: Data of 112 children aged between 6-12 years was analyzed. Hypertension (BP >percentile 95) was detected in 2.7% and pre hypertension (BP in percentiles 90-95) in 3.6% of thesample. Children with abnormal BP had higher levels of usCRP (p <0.05) and a non significant tendency towards a higher body mass index. All hypertensive and one pre hypertensive children had FH of AHT. Eleven percent of parents, had high blood pressure. In no children, both parents werehypertensive. Children with a family history of hypertension had higher concentrations of total serum cholesterol (p <0.05). Conclusions: The abnormal prevalence of AHT found in this study is comparable to other studies. FH associated to higher levels of BP in children. Children withabnormal BP had a higher subclinical level of inflammation.

Analysis of genetic and non-genetic factors that affect the QTc interval in a Mongolian population: the GENDISCAN study

The QTc interval is a complex quantitative trait and a strong prognostic indicator of cardiovascular mortality in general, healthy people. The aim of this study was to identify non-genetic factors and quantitative trait loci that govern the QTc interval in an isolated Mongolian population. We used multiple regression analysis to determine the relationship between the QTc interval and non-genetic factors including height, blood pressure, and the plasma lipid level. Whole genome linkage analyses were performed to reveal quantitative trait loci for the QTc interval with 349 microsatellite markers from 1,080 Mongolian subjects. Among many factors previously known for association with the QTc interval, age, sex, heart rate, QRS duration of electrocardiogram and systolic blood pressure were also found to have influence on the QTc interval. A genetic effect for the QTc interval was identified based on familial correlation with a heritability value of 0.31. In a whole genome linkage analysis, we identified the four potential linkage regions 7q31-34, 5q21, 4q28, and 2q36.

La vía transduccional Rho A y Rho kinasa está activada en la pared arterial de ratas con niveles genéticamente elevados de angiotensina II / Transductional Rho A and Rho kynase pathways are activated in the arterial wall of rats with genetically elevated levels of angiotensin II

Antecedentes: El polimorfismo de la enzima convertidora de angiotensina I (ECA) determina mayor actividad de ECA yniveles de angiotensina (Ang) II en ratas Brown Norway (BN) y menor actividad de ECA y niveles de Ang II en ratas Lewis (L). La relación entre niveles de Ang II y la vía transduccional Rho A/Rho kinasa no ha sido explorada.Objetivo: Determinar la participación de la vía Rho A/ Rho kinasa mediante la fosforilación de la proteína blanco 1 de la fosfatasa de la miosina (MYPT1) vascular en ratas con niveles genéticamente bajos (L) y altos de Ang II (BN) y su relación con la expresión de algunos genes que determinan remodelado de la pared arterial: el gen del activador de plasminógeno 1 (PAI-1), el gen de la proteína quimioatractante de monocitos (MCP-1) y el gen del factor de transformación beta 1 (TGF- b1) en la pared arterial. Métodos: Se usaron ratas machos homocigotos de 150 grs BN y L. Para inhibir la vía Rho A / Rho kinasa, se administró fasudil (100 mg/Kg/día por gavage) a ratas BN, durante 7 días. Se determinó la presión arterial sistólica (PAS), la expresión vascular (en la aorta) de MYPT1 total (MYPT1-T) y MYPT1 fosforilada (MYPT1-P) y la relación entre ambas por Western blot además de la expresión génica de PAI-1, MCP-1 y de TGF-b1 por RT-PCR (en unidades de densidad óptica). Resultados como promedio(ES): El antagonista del receptor tipo I de angiotensina II Candesartán por 7 días (10 mg/Kg/d, n = 8) redujo en un 50 por ciento los niveles elevados de MYPT1-P/T en las ratas BN (p <0.05) sin modificar la mayor expresión de los genes evaluados. Conclusión: La vía Rho A/ Rho kinasa se encuentra activada en la pared arterial de ratas con niveles elevados de Ang II (BN) y causa mayor expresión génica de PAI-1 y de MCP-1 ya que la sobre expresión de ambos tiende a normalizarse con fasudil. La mayor expresión génica de TGF-b1 en la aorta en ratas BN parece no estar relacionada con la activación de de Rho A/ Rho kinasa vía Angiotensina II ya que no...

Factores de riesgo de resistencia insulínica en escolares de 7 a 12 años / Factors of risk of resistance insulin in school of 7 to 12 years

La presencia de factores de riesgo tales como: obesidad, dislipidemias e hipertensión arterial (HTA), entre otros, alertan sobre la posibilidad del desarrollo, a corto y largo plazo, de resistencia insulínica. Estos factores se inician durante la infancia. Identificar los factores de riesgo de resistencia insulínica en escolares de 7 a 12 años. Estudio descriptivo y transversal en 33 escolares de ambos sexos, a los cuales se les realizó un cuestionario sobre los antecedentes familiares y personales relacionados con los factores de riesgo asociados al desarrollo de resistencia insulínica. Además, se resgistró en cada escolar los datos antropométricos para el cálculo del IMC y la toma de la tensión arterial (TA). En los antecedentes familiares se detectó que el 9.09 por ciento eran hijos de madres diabéticas y en todos ellos se evidenció antecedentes de diabetes, hipertensión, obesidad y dislipidemía en otros familiares. En el 36,37 por ciento, 72,72 por ciento, 30,30 por ciento y 42,42 por ciento se halló antecedentes de diabetes, HTA, obesidad y dislipidemías familiar, respectivamente. El 60,60 por ciento presentaba más de los factores de riesgo familiares simultáneos. El 15,15 por ciento de los escolares fueron pequeños para su edad gestacional, de los cuales el 60 por ciento mostraron además, antecedentes familiares de diabetes, hipertensión, obesidad y dislipidemia; y en el 20 por ciento se halló cifras de TA elevadas. Se detectó HTA en el 9.09 por ciento de los escolares, quienes presentaron otros antecedentes familiares. El IMC no mostró niños obesos, no obstante, reveló que el 9.09 por ciento presentaba sobrepeso con antecedentes de hipertensión y obesidad familiar. En los escolares estudiados se detectaron diversos factores de riesgo relacionados con la resistencia insulínica. Se recomienda la detección y monitorización de estos factores de riesgo como parte del seguimiento rutinario de los niños escolares.

Blood pressure response to cold pressor test in siblings of hypertensives.

One hundred and five female and thirty-four male student volunteers were divided into three groups. Each group was again divided into siblings of hypertensives (SH) and siblings of normotensives (C). SH group had higher basal seated and supine Systolic and Diastolic Blood Pressures (SBPs and DBPs, respectively). During cold pressor test (CPT), the SH group showed higher rise of SBPs and DBPs. All the volunteers were again regrouped as hyperreactors (HR) (the criteria of a rise of more than 22 mmHg systolic and 18 mmHg diastolic blood pressure during (CPT) and normoreactors (NR). HR showed higher resting seated SBPs and DBPs, and higher rise of SBPs & DBPs during CPT as compared to control groups. The rise in SBPs and DBPs in hyperreactors was significantly higher than SH groups only in 16-19 years female group. The rise of SBPs and DBPs during CPT were also higher in HR as compared to NR of all age groups. The rise of SBPs and DBPs during CPT was significantly higher in controls than in NR in the two female groups. The study suggests that identification of hyperreactors in population gives a better indication of potential hypertensives of future than the children of hypertensives.