We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (∼9% in WKY and SHR) and MAP reductions (−8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (−13%) and arteriolar wall/lumen ratio (−35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

BackgroundExercise training (T) blunts functional deficits and renin-angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular-controlling areas.Methods and ResultsSpontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) were trained for 0, 1, 2, 4, 8 and 12 weeks. Sedentary (S) groups served as time-controls. After arterial pressure (AP) and heart rate (HR) recordings at rest, fresh and fixed brains were harvested for qPCR and immunofluorescence assays. SHR-S vs. WKY-S exhibited higher mean AP (MAP) and HR, increased pressure variability and sympathetic activity, elevated AT1 receptor (AT1) expression in nucleus tractus solitarii (NTS) and higher Mas receptor expression in the rostroventrolateral medulla (RVLM). In SHR, T promptly (T2 on) reduced sympathetic variability to heart/vessels and largely decreased angiotensinogen expression in the paraventricular hypothalamic nucleus (PVN) and NTS, with a late RVLM reduction (T4). AT1 expression was only reduced at T12 (PVN and NTS) with transient, not maintained Mas receptor changes in PVN and RVLM. These responses were accompanied by baseline MAP and HR reduction in the SHR-T (from T4 on). In the SHR group, PVN angiotensinogen expression correlated positively with sympathetic activity, resting MAP and HR. In WKY-T, a precocious (T2-T12) RVLM AT1 decrease preceded the appearance of resting bradycardia (from T8 on).ConclusionsEarly and maintained reduction of angiotensinogen content in autonomic areas of the SHR is the most prominent effect of training on brain RAS. Down-regulation of PVN RAS expression is an essential factor to drive cardiovascular benefits in SHR-T, while resting bradycardia in WKY-T is correlated to RVLM AT1 reduction.

Prolonged and continuous exposure of mammals to a low oxygen environment (chronic hypoxia) elicits remarkable morphological and physiological adjustments. These include altered gene expression, increased peripheral chemosensitivity, enhanced respiratory drive and sympathoexcitation. The current study examines the hypothesis that acute hypoxia (AH) initiates an immune response in the central nervous system elicited by an increased expression of inflammatory mediators in specific brain areas related to autonomic control. Male Wistar rats pretreated with vehicle or minocycline (30 mg kg day for 5 days) were subjected to AH (8% O , balance N ) or normoxia (21% O ) for 3 h. AH increased interleukin (IL)-6, IL-1β and matrix metalloprotease 9 (MMP9) mRNA expression in the paraventricular nucleus of the hypothalamus (PVH) and rostral ventrolateral medulla (RVLM) and tumour necrosis factor α (TNFα) in the RVLM. Treatment with minocycline, an inhibitor of microglial activation, decreased IL-1β, TNFα and MMP9 mRNA expression in the RVLM, and increased IL-6 mRNA expression in the RVLM and PVH of rats exposed to AH. Minocycline treatment also elicited a decrease in the number of activated neurons in the RVLM/C1 neurons (expressed as Fos /tyrosine hydroxylase ), the number of Fos-activated neurons in the PVH and the increase in ventilation elicited by AH. When viewed together, these results suggest that AH modulates the expression of inflammatory mediators in autonomic brain nuclei that may be involved in the responses to chemoreceptor activation.

We evaluated herein whether diet‐induced obesity alters sympathovagal balance, blood pressure, and neuropeptides levels at the hypothalamus and brainstem of mice. Male C57BL6J mice fed with a high‐fat (HFD) or a high‐fat high‐sucrose (HFHSu), or a regular chow diet (C) for 8 weeks were evaluated for metabolic parameters and blood pressure, the latter being performed in conscious freely moving mice. Spectral analysis from the records of systolic blood pressure (SBP) and cardiac pulse intervals (PI) was performed to analyse the autonomic balance in the cardiovascular system. HFD‐fed mice developed two distinct hemodynamic phenotypes: hypertensive mice (HFD‐H) with high systolic and diastolic BP levels and hypertension‐resistant mice (HFD‐R) whose BP levels were similar to C group. Spectral analysis of SBP and PI variabilities indicate that the low‐frequency (LF)/high‐frequency (HF) ratio, which is an index of sympathovagal balance, is higher in HFD‐H compared to HFD‐R. Along with hypertension and higher LF/HF ratio, HFD‐H mice presented increased hypothalamic mRNA levels of cocaine‐ and amphetamine‐regulated transcript (CART), and increased CART‐positive neurones in the dorsomedial hypothalamus (DMH) by high‐fat diet when compared to C group. Despite developing obesity to similar levels than HFD feeding, intake of a HFHSu was not associated with hypertension in mice neither CART levels increase. Collectively, our main findings indicate that high‐fat diet induced‐hypertension and autonomic imbalance are associated to an upregulation of CART levels in the DMH of mice.

Brazil is a large country with a population of nearly 200 million people. There are difficulties in providing public health education. To ensure its effectiveness, health education should begin during adolescence, to encourage young people to adopt healthy habits. A web-based tele-education platform was developed. Thirty students from a public high school in the rural city of Tatui took part in a pilot trial. Six teachers coordinated the student's activities. After face-to-face training, the students participated in tele-education, using a ‘cybertutor’ (an educational environment based on the website) and discussion lists. There were 15 face-to-face interactions, followed by more than 200 offline and 50 online interactions. The students learned about seven health topics. During the following year, 20 of the students used their knowledge to teach people from their local communities. We estimate that about 3000 people, including children, adults and the elderly, received public health education during events in Tatui and in their schools. The pilot trial showed that face-to-face and distance interventions in the rural city of Tatui were a feasible method of disseminating public health information.

A hipertensão arterial encontra-se intimamente relacionada com hiperatividade do sistema renina-angiotensina (SRA). Dados anteriores do nosso laboratório demonstraram que: a) a elevação da pressão arterial (PA) era acompanhada da ativação da angiotensina II plasmática e tecidual; b) a expressão de RNAm de angiotensinogênio e receptores AT 1 em áreas bulbares encontravamse aumentadas na hipertensão induzida por coarctação e na hipertensão espontânea (SHR) em ratos; c) o treinamento aeróbio de baixa intensidade (T) de 12 semanas mostrou-se eficaz em reduzir a expressão de angiotensinogênio (Aogen) no núcleo do trato solitário (NTS) de SHR. Não há, no entanto, informações relativas aos efeitos seqüenciais do treinamento sobre a expressão de outros componentes do SRA bem como em outras áreas centrais de controle autonômico. No presente projeto avaliamos em SHR e seus controles normotensos (WKY) a seqüência temporal dos efeitos do treinamento aeróbio de baixa intensidade sobre: 1) as respostas funcionais (pressão arterial, PA e freqüência cardíaca, FC), 2) a expressão de RNAm de Aogen e receptores AT 1 (AT 1 R) nos núcleos paraventricular do hipotálamo (PVN), do trato solitário (NTS) e na região rostro-ventrolateral do bulbo (RVL), 3) a expressão protéica de Aogen e AT 1 R nos mesmos núcleos. Ratos WKY e SHR, com 3 meses, foram submetidos a T (50-60% da capacidade máx.; 5 dias/sem; 1 h/dia) ou mantidos sedentários (S) por 0, 1, 2, 4, 8 ou 12 semanas. Nos diferentes tempos experimentais os ratos foram cateterizados para o registro da PA e FC basais, e, a seguir perfundidos com salina (coleta de "punches" do PVN, NTS e RVL para se determinar a expressão do Aogen e AT 1 R pelo RT-PCR em tempo real) ou PFA 4% (cortes seqüenciais das áreas de interesse para Imunofluorescência para Aogen e AT 1 R com co-localização de NeuN em neurônios). SHR (vs WKY) apresentaram PA e FC elevadas (174±2 vs 123±2 mmHg; 385±7 vs 326±4 b/min) e maior expressão gênica de AT 1 R no NTS (+67%, p<0,05). T aumentou a capacidade física e causou bradicardia de repouso em ambos os grupos, mas a PA foi reduzida apenas nos SHR (queda de 6,5% de T 8 à T 12 , p<0,05). Nos SHR, T reduziu a expressão de RNAm do Aogen no PVN (-34% em T 2 ) e NTS (-30% em T 4 ), reduzindo também a expressão de RNAm de AT 1 R apenas em T 12 (-56% e -39%, respectivamente para PVN e NTS). Nos WKY, T determinou redução da expressão gênica de Aogen e AT 1 R no RVL a partir de T 8 (-49% e -58%, respectivamente). A imunofluorescência para Aogen e AT 1 R indicou a localização destas proteínas no PVN, NTS e RVL, confirmando qualitativamente as alterações de conteúdo induzidas pelo T em SHR e WKY. Em síntese, nossos dados indicam que a queda de PA e a instalação da bradicardia de repouso (efeitos benéficos do treinamento aeróbio de baixa intensidade) são progressivos e aparecem mais precocemente nos SHR que nos WKY. Além disso, são acompanhadas/ precedidas de redução da expressão gênica e protéica de Aogen no PVN e NTS dos SHR e da redução da expressão gênica e protéica de Aogen e AT ...

CHAAR, L. J. High blood pressure and autonomic dysfunction induced by highfat diet: role of CART and inflammatory factors in central autonomic network. 2016, 144 p. Thesis (PhD in Human Physiology).

To evaluate the effects of hypertension and T in the microcirculatory profile within autonomic areas, WKY and SHR were submitted to treadmill T (55% of maximum capacity, 1h/day, 5 d/week) or kept sedentary (S) for 3 months. After hemodynamic measurements at rest, rats were anesthetized for FITC‐dextran administration (1 ml of 5% solution). Brains were removed, post‐fixed and sliced (25 μm) for analysis of the capillary volume (Image ProPlus + 3D‐construction) within the NTS and hypothalamic paraventricular nucleus (PVN). SHR vs. WKY exhibited elevated MAP and HR (180±2 mmHg, 359±6 b/min). Capillary volume (expressed as ×10−3μm3/μm3 tissue) was similar in WKY‐S and SHR‐S but differed between autonomic areas being larger into the PVN (ventromedial=14.15±1.27, posterior=6.72±0.56) and smaller into the NTS (2.51±0.14). T improved treadmill performance and resting bradycardia (−9%) in both groups; pressure fall (−8%) was only observed in the SHR. T caused marked increase in capillary volume in all autonomic areas (ventromedial: +91% and +74%; posterior: +20% and +21%; NTS: +41% and +27%, for WKY and SHR respectively). Contrary to the peripheral microcirculatory response, hypertensive brain capillaries showed no rarefaction within autonomic areas. Data also showed a large T‐induced capillary angiogenesis in both groups, therefore improving brain perfusion after training. Financial Support: CAPES, FAPESP