Oxidative stress may explain how hypertension is maintained by normal levels of angiotensin II

It is well known that essential hypertension evolves in most patients with "near normal" levels of plasma renin activity. However, these levels appear to be responsible for the high levels of arterial pressure because they are normalized by the administration of angiotensin II converting inhibitors or angiotensin receptor antagonist. In experimental animals, hypertension can be induced by the continuous intravenous infusion of small doses of angiotensin II that are not sufficient to evoke an immediate pressor response. However, this condition resembles the characteristics of essential hypertension because the high levels of blood pressure exist with normal plasma levels of angiotensin II. It is suggested that small amounts of angiotensin whose plasma levels are inappropriate for the existing size of extracellular volume stimulate oxidative stress which binds nitric oxide forming peroxynitrite. The latter compound oxidizes arachidonic acid producing isoprostaglandin F2a (an isoprostane) which is characterized by a strong antinatriuretic vasoconstrictor renal effect. In this chain of reactions the vasoconstrictor effects derived from oxygen quenching of nitric oxide and increased isoprostane synthesis could explain how hypertension is maintained with normal plasma levels of renin.

A high-fructose diet induces insulin resistance but not blood pressure changes in normotensive rats

Rats fed a high-fructose diet represent an animal model for insulin resistance and hypertension. We recently showed that a high-fructose diet containing vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver and muscle of normal rats. In the present study, we examined the mean blood pressure, serum lipid levels and insulin sensitivity by estimating in vivo insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml of 6 µg insulin, iv) followed by calculation of the rate constant for plasma glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high-fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1 sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K for the control and high-fructose diets had no effect on insulin sensitivity measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats receiving the control and high-fructose diets from 117 ± 3 and 118 ± 3 mmHg to 141 ± 4 and 132 ± 4 mmHg (P<0.05), respectively. Triacylglycerol levels were higher in both groups treated with a high-fructose diet when compared to controls (C 1:3 R Na:K: 1.2 ± 0.1 mmol/l vs F 1:3 R Na:K: 2.3 ± 0.4 mmol/l and CNa 1:1 R Na:K: 1.2 ± 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 ± 0.4 mmol/l, P<0.05). These data suggest that fructose alone does not induce hyperinsulinemia or hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in the diet may contribute to the elevated blood pressure in this animal model.

Respiratory mechanics and morphometric changes during anesthesia with ketamine in normal rats

Ketamine is believed to reduce airway and pulmonary tissue resistance. The aim of the present study was to determine the effects of ketamine on the resistive, elastic and viscoelastic/inhomogeneous mechanical properties of the respiratory system, lungs and chest wall, and to relate the mechanical data to findings from histological lung analysis in normal animals. Fifteen adult male Wistar rats were assigned randomly to two groups: control (N = 7) and ketamine (N = 8). All animals were sedated (diazepam, 5 mg, ip) and anesthetized with pentobarbital sodium (20 mg/kg, ip) or ketamine (30 mg/kg, ip). The rats were paralyzed and ventilated mechanically. Ketamine increased lung viscoelastic/inhomogeneous pressure (26%) compared to the control group. Dynamic and static elastances were similar in both groups, but the difference was greater in the ketamine than in the control group. Lung morphometry demonstrated dilation of alveolar ducts and increased areas of alveolar collapse in the ketamine group. In conclusion, ketamine did not act at the airway level but acted at the lung periphery increasing mechanical inhomogeneities possibly resulting from dilation of distal airways and alveolar collapse.

Ambulatory blood pressure and Doppler echocardiographic indexes of borderline hypertensive men presenting an exaggerated blood pressure response during dynamic exercise

Borderline hypertension (BH) has been associated with an exaggerated blood pressure (BP) response during laboratory stressors. However, the incidence of target organ damage in this condition and its relation to BP hyperreactivity is an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a group of BH men (N = 36) according to office BP measurements with exaggerated BP in the cycloergometric test. A group of normotensive men (NT, N = 36) with a normal BP response during the cycloergometric test was used as control. To assess vascular function and reactivity, all subjects were submitted to the cold pressor test. Before Doppler echocardiography, the BP profile of all subjects was evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group presented normal monitored levels of BP. In contrast, 19 subjects from the original BH group presented normal monitored BP levels and 17 presented elevated monitored BP levels. In the NT group all Doppler echocardiographic indexes were normal. All subjects from the original BH group presented normal left ventricular mass and geometrical pattern. However, in the subjects with elevated monitored BP levels, fractional shortening was greater, isovolumetric relaxation time longer, and early to late flow velocity ratio was reduced in relation to subjects from the original BH group with normal monitored BP levels (P<0.05). These subjects also presented an exaggerated BP response during the cold pressor test. These results support the notion of an integrated pattern of cardiac and vascular adaptation during the development of hypertension.

Reflex control of arterial pressure and heart rate in short-term streptozotocin diabetic rats

Impaired baroreflex sensitivity in diabetes is well described and has been attributed to autonomic diabetic neuropathy. In the present study conducted on acute (10-20 days) streptozotocin (STZ)-induced diabetic rats we examined: 1) cardiac baroreflex sensitivity, assessed by the slope of the linear regression between phenylephrine- or sodium nitroprusside-induced changes in arterial pressure and reflex changes in heart rate (HR) in conscious rats; 2) aortic baroreceptor function by means of the relationship between systolic arterial pressure and aortic depressor nerve (ADN) activity, in anesthetized rats, and 3) bradycardia produced by electrical stimulation of the vagus nerve or by the iv injection of methacholine in anesthetized animals. Reflex bradycardia (-1.4 ± 0.1 vs -1.7 ± 0.1 bpm/mmHg) and tachycardia (-2.1 ± 0.3 vs -3.0 ± 0.2 bpm/mmHg) were reduced in the diabetic group. The gain of the ADN activity relationship was similar in control (1.7 ± 0.1% max/mmHg) and diabetic (1.5 ± 0.1% max/mmHg) animals. The HR response to vagal nerve stimulation with 16, 32 and 64 Hz was 13, 16 and 14% higher, respectively, than the response of STZ-treated rats. The HR response to increasing doses of methacholine was also higher in the diabetic group compared to control animals. Our results confirm the baroreflex dysfunction detected in previous studies on short-term diabetic rats. Moreover, the normal baroreceptor function and the altered HR responses to vagal stimulation or methacholine injection suggest that the efferent limb of the baroreflex is mainly responsible for baroreflex dysfunction in this model of diabetes.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Exogenous normal lymph alleviates microcirculation disturbances and abnormal hemorheological properties in rats with disseminated intravascular coagulation

Disturbances of the microcirculation and abnormal hemorheological properties are important factors that play an important role in disseminated intravascular coagulation (DIC) and result in organ dysfunction or failure. In the present study, we established an animal model of DIC using intravenous Dextran 500 in rats, and used exogenous normal lymph corresponding to 1/15 of whole blood volume for injection through the left jugular vein. We found that normal lymph could improve the blood pressure and survival time of rats with DIC. The results regarding the mesenteric microcirculation showed that the abnormality of the diameter of mesenteric microvessels and micro-blood flow speed in the DIC+lymph group was significantly less than in the DIC+saline group. Whole blood viscosity, relative viscosity, plasma viscosity, hematocrit (Hct), erythrocyte sedimentation rate (ESR), and electrophoresis time of erythrocytes were significantly increased in the DIC+saline group compared to the control group. The electrophoretic length and migration of erythrocytes from the DIC+saline and DIC+lymph groups were significantly slower than the control group. Blood relative viscosity, Hct, ESR, and electrophoretic time of erythrocytes were significantly increased in the DIC+lymph group compared to the control group. Whole blood viscosity, relative viscosity and reduced viscosity were significantly lower in the DIC+lymph group than in the DIC+saline group, and erythrocyte deformability index was also significantly higher than in the DIC+saline and control groups. These results suggest that exogenous normal lymph could markedly improve the acute microcirculation disturbance and the abnormal hemorheological properties in rats with DIC induced by Dextran 500.

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Testes de padrão de freqüência e de duração em idosos com sensibilidade auditiva normal

Estudos atuais apontam para o fato que o indivíduo idoso pode apresentar uma desordem do processamento auditivo mesmo sem haver uma lesão estrutural que a explique diretamente. OBJETIVO: Caracterizar o desempenho de idosos com sensibilidade auditiva normal no Teste de Padrão de Freqüência (TPF) e de Padrão de Duração (TPD). FORMA DE ESTUDO: Clínico prospectivo. MÉTODO: A amostra contou com 25 idosos com audição normal e sem história de comprometimentos centrais. Foram realizados os Testes de Padrão de Duração e Teste de Padrão de Freqüência a 50dBNS, sendo solicitada resposta através de nomeação. RESULTADOS: Não foram encontradas diferenças nos dois testes, segundo a variável lado da orelha. A porcentagem média de acertos obtida no Teste de Padrão de Duração foi de 67,5% e no Teste de Padrão de Freqüência foi de 49,2%. A correlação entre os testes TPD e TPF e a idade dos pacientes mostrou-se inversamente proporcional, ou seja, quanto maior a idade pior o desempenho nos testes, sendo que a maior correlação foi encontrada no Teste de Padrão de Duração. CONCLUSÃO: Não foram observadas diferenças segundo a variável lado da orelha e os indivíduos idosos com sensibilidade auditiva normal apresentam uma porcentagem média de acertos de 47,2% no Teste de Padrão de Freqüência de 67,5% no Teste de Padrão Duração.

Avaliação de pacientes com queixa de tontura e eletronistagmografia normal por meio da estabilometria

As causas de tontura são de difícil diagnóstico. Atualmente dispomos de uma variedade de exames complementares, contudo, nenhum avalia bem a função vestibular. Os testes mais utilizados para este fim são as provas eletronistagmográficas e posturográficas. OBJETIVO: O objetivo do trabalho foi o de analisar os resultados da estabilometria de pacientes com queixa de tontura que apresentaram eletronistagmografia normal e compará-los aos de um grupo controle. FORMA DE ESTUDO: Prospectivo, do tipo seccional transversal. MATERIAL E MÉTODO: Realizou-se no SME do Serviço de Otorrinolaringologia do HUCFF/UFRJ. No total foram avaliados 22 pacientes (15 mulheres e sete homens) com idade média de 47,6±9 anos. O grupo controle foi de 25 sujeitos saudáveis (18 mulheres e sete homens) com idade média de 46,8±7 anos. Todos os indivíduos foram submetidos à estabilometria com os olhos abertos, em seguida por olhos fechados, durante 30 segundos cada. RESULTADOS: O grupo de pacientes apresentou resultados estatisticamente significativos em todos os parâmetros estabilimétricos avaliados quando comparados ao grupo controle. Na comparação dos resultados com os olhos fechados e abertos, apenas a velocidade média ântero-posterior no grupo controle foi significativa. CONCLUSÃO: Conclui-se que o grupo de pacientes apresentou resultados estatisticamente significativos em relação ao grupo controle em todos os parâmetros estabilométricos analisados, demonstrando, assim, que o grupo de pacientes com queixa de tontura apresentou maior instabilidade na posição ortostática do que o grupo de sujeitos saudáveis.

Zumbido em pacientes com audiometria normal: caracterização clínica e repercussões

Pacientes com zumbido e audiometria normal constituem um grupo importante, pois seus achados não sofrem influência da perda auditiva. Apesar disso, este grupo é pouco estudado e não sabemos se suas características clínicas e repercussões são semelhantes às dos indivíduos com perda auditiva. OBJETIVOS: Comparar as características clínicas do zumbido e sua interferência nas atividades diárias em pacientes com e sem perda auditiva. FORMA DE ESTUDO: coorte histórica. MATERIAL E MÉTODO: Entre 744 pacientes atendidos no Grupo de Pesquisa em Zumbido do HCFMUSP, avaliou-se retrospectivamente com um corte transversal os 55 indivíduos com audiometria tonal normal. O grupo controle correspondeu a 198 pacientes com zumbido e perda auditiva atendidos sob o mesmo protocolo. Analisou-se os dados dos pacientes, as características clínicas do zumbido e sua repercussão na vida do paciente. RESULTADOS: A idade média no grupo de estudo (43,1 ± 13,4 anos) foi significantemente menor do que a do grupo controle (49,9 ± 14,5 anos). Em ambos os grupos houve predomínio do sexo feminino e o zumbido foi predominantemente bilateral, único e constante, porém sem diferença entre os grupos. A interferência na concentração e no equilíbrio emocional foi significantemente menor no grupo de estudo (25,5% e 36,4%) do que no controle (46% e 61,6%), porém sem diferença quanto à interferência no sono e na atividade social. CONCLUSÕES: O grupo de pacientes com zumbido e audição normal apresentou características clínicas semelhantes em relação ao grupo com perda auditiva. Entretanto, a faixa etária acometida e a interferência sobre a concentração e o equilíbrio emocional foram significantemente menores nestes.

Audiometria de alta freqüência em adultos jovens e mais velhos quando a audiometria convencional é normal

A audiometria de alta freqüência é capaz de detectar precocemente alterações em sensibilidade advindas de processos como o envelhecimento. Seu uso é limitado, o que recomenda estudos para esclarecer seu desempenho, especialmente entre adultos de mais idade. OBJETIVO: Comparar os limiares para as freqüências de 250Hz a 16kHz, entre adultos jovens e mais velhos normoacúsicos, com e sem queixa audiológica. CASUÍSTICA E MÉTODO: A sensibilidade a tons puros de 250Hz a 16kHz foi avaliada com audiômetro AC-40, em 64 adultos, igualmente distribuídos: jovens (25 a 35 anos) e mais velhos (45 a 55 anos) de ambos os gêneros, com forma de estudo de coorte transversal. RESULTADOS: Os adultos mais velhos apresentaram limiares mais elevados em todas as freqüências, mais significativamente nas mais altas (8 a 16kHz), quando comparados com os adultos jovens. Homens apresentaram limiares mais elevados do que mulheres entre 3 e 10kHz. CONCLUSÃO: O processo de envelhecimento auditivo, envolvendo perda de sensibilidade auditiva para altas freqüências, pode ser detectado em idades anteriores às tipicamente pesquisadas, uma vez que a audiometria de alta freqüência demonstrou ser instrumento importante para distinguir a sensibilidade auditiva entre adultos jovens e mais velhos, quando audiologicamente normais.

Do estudo dos potenciais de média latência eliciados por logon em sujeitos do sexo feminino com audição normal

Os potenciais de média latência são potenciais auditivos que ocorrem entre 10ms a 80ms, formados por ondas polifásicas positivas e negativas denominadas de N0, P0, Na, Pa, Nb e Pb. O logon é um estímulo acústico que permite eliciar respostas de média latência ativando regiões específicas da cóclea. Sua vantagem sobre o clique é a possibilidade avaliar as áreas de baixa freqüência (abaixo de 1kHz). OBJETIVO: O objetivo deste trabalho foi verificar a resposta eletrofisiológica das MLR estimulados por logon nas freqüências de 500, 1000 e 2000 Hz. CASUÍSTICA E MÉTODO: Forma de estudo prospectivo e descritivo de uma amostra de 14 voluntárias do sexo feminino, normais dos pontos de vista otológico e audiológico convencional. O estímulo foi monoaural e ipsilateral à derivação de captação dos potenciais (Cz/A1-2). RESULTADOS: O complexo NaPa foi o mais facilmente identificado e esteve presente em 100% dos exames realizados a 2000 Hz e em 96,4% a 500 e 1000 Hz. CONCLUSÕES: As MLR podem se eliciadas pelo logon nas freqüências de 500, 1000 e 2000 Hz; o complexo NaPa foi o evento prevalente das MLR e o estímulo logon a 2000 Hz eliciou maior número de respostas do que as outras freqüências.