Angiotensin II AT2 Receptors Contribute to Regulate the Sympathoadrenal and Hormonal Reaction to Stress Stimuli.

Angiotensin II, through AT1 receptor stimulation, mediates multiple cardiovascular, metabolic, and behavioral functions including the response to stressors. Conversely, the function of Angiotensin II AT2 receptors has not been totally clarified. In adult rodents, AT2 receptor distribution is very limited but it is particularly high in the adrenal medulla. Recent results strongly indicate that AT2 receptors contribute to the regulation of the response to stress stimuli. This occurs in association with AT1 receptors, both receptor types reciprocally influencing their expression and therefore their function. AT2 receptors appear to influence the response to many types of stressors and in all components of the hypothalamic-pituitary-adrenal axis. The molecular mechanisms involved in AT2 receptor activation, the complex interactions with AT1 receptors, and additional factors participating in the control of AT2 receptor regulation and activity in response to stressors are only partially understood. Further research is necessary to close this knowledge gap and to clarify whether AT2 receptor activation may carry the potential of a major translational advance.

Beneficial effects of Angiotensin II receptor blockers in brain disorders.

A canonical brain Renin-Angiotensin System (RAS), like the canonical peripheral RAS, has long been proposed as a major regulator of brain function. Because of methodological limitations, however, this system is in urgent need of critical revision. The Angiotensin II AT1 receptors have been confirmed as key factors in the regulation of brain function, and AT1 receptor over activity has been established as a major and early injury factor in the development of many brain diseases. Consequently, Angiotensin Receptor Blockers (ARBs), compounds widely used to treat cardiovascular and metabolic disorders, are excellent candidates for repurposing for the treatment of brain disorders. This review will discuss some of the reasons why revisiting brain RAS is a pressing necessity, will present evidence for a participation of AT1 receptor over activity in the development of major brain disorders, and will present definite evidence of ARBs neuroprotective effects. The review will focus on the beneficial effects of ARB therapy in stroke, neurodegenerative disorders including Alzheimer's and Parkinson's diseases, traumatic brain injury, radiation- induced brain damage, stress and mood disorders.

Prediction of correlates of daily physical activity in Spanish children aged 8-9 years.

The aims of the study were (a) to examine the associations between the daily physical activity (PA) of 8- to 9-year-old children and their parents, and (b) to examine what effect the child's daily PA has on its cardiorespiratory fitness (CRF), body mass index (BMI), and health-related quality of life (HRQoL). The sample consisted of 1021 persons [351 children (8.73 ± 0.69 years in age) and 670 parents]. Pedometers were used to evaluate PA in parents and their children over the course of 4 days (Thursday-Sunday), with the instructions on how to wear the pedometers for 24 h a day. Also evaluated were height, weight, BMI, CRF (via the maximal multistage 20-m shuttle run test), and HRQoL (via the EQ-5D-Y questionnaire). Associations between these variables were studied using path model techniques. The father's PA predicts his child's daily PA. This in turn predicts the child's lower BMI, CRF, and perceived quality of life. The findings suggest that the role model of a physically active father positively influences the child's PA habits, and hence that the family environment can have an important part to play in promoting health.

Prospective double-blind clinical trial evaluating the effectiveness of Bromelain in the third molar extraction postoperative period.

OBJECTIVES: To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. STUDY DESIGN: This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received Bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. RESULTS: Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received Bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. CONCLUSIONS: Further studies are necessary to analyze different administration patterns and doses of Bromelain for the use in the postoperative of impacted third molars.

Measurements on the external load acting on aquatic resistance fins during flexion/extension movements using a robotic joint.

Aquatic resistance training has been proven to be beneficial to many people, in particular those struggling with degenerative joint diseases or recovering from other musculoskeletal issues as the reaction forces acting on the joints become lower, but without compromising the cardiovascular and neuromuscular benefit of the movement. Little has been written on the load produced by or measurements of the devices used in aquatic resistance training. Therefore, uncertainties exist regarding details of how much load can be applied onto the foot when performing the movements and how to quantify progression. In this study, an instrumented robotic arm was designed, built, and used to measure the load acting on the three different types of fins during a simulated flexion/extension movement of a knee. The angular velocities of the knee ranged from 25°/s to 150°/s, which represent the physiological range of in vivo movements. The results demonstrated that the load followed a second-order polynomial with the angular velocities. The load is therefore a function of the angular velocity, the surface area of the fins, and the location of the fins away from the joint center rotation. We modeled the progression of speeds at maximal voluntary movements based on previous studies. The maximum loads measured between 11 kg and 13 kg in extension and 6 kg and 9 kg in flexion at 150°/s rotational velocity.

High angiotensin-converting enzyme activity in the neurohypophysis of Brattleboro rats.

The activity of angiotensin-converting enzyme is significantly higher in the intermediate and posterior pituitary lobes of Brattleboro rats than in Long-Evans control rats. The high activity level was reversed by vasopressin treatment. Conversely, angiotensin-converting enzyme activity was significantly lower in the anterior pituitary of Brattleboro rats than in Long-Evans rats, and this activity level was not affected by vasopressin. these findings suggest an inverse relation between vasopressin and angiotensin systems in the posterior and intermediate lobes of the pituitary gland.

Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro.

The use of a sensitive enzymatic assay demonstrates that tryptamine occurs normally in rat brain. Intracisternal administration of [(14)C]tryptamine results in the formation of N-methyl-and dimethyltryptamine(a psychotomimetic compound)in the rat brain. An enzyme that converts tryptamine and N-methyl-tryptamine to N-methyl-and dimethyltryptamine was found to be present in rat and human brain. The N-methylation of tryptamine was inhibited by normally occurring compounds present in rat brain.

Adrenaline-forming enzyme in brainstem: elevation in genetic and experimental hypertension.

The adrenaline-forming enzyme (phenylethanolamine N-methyltransferase) was elevated in the A1 and A2 regions of the brainstem of 4-week-old spontaneously (genetic) hypertensive rats and in the A1 region of adult experimentally (deoxycorticosterone acetate and sodium chloride) hypertensive rats. The administration of a phenylethanolamine N-methyltransferase inhibitor to experimentally hypertensive animals caused a reduction of the elevated blood pressure to normal values. These results implicate adrenaline-containing neurons in the brainstem in the development of hypertension.

Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites.

The zona reticulata, the subdivision of the substantia nigra containing dendrites of the dopaminergic nigro-neostriatal neurons, contains dopamine-sensitive adenylate cyclase activity. This nigral dopamine receptor is similar to the striatal dopamine receptor. These and previous data suggest a physiological role (or roles) for dopamine in the substantia nigra.

Phenylethanolamine: a new putative neurotransmitter in Aplysia.

Phenylethanolamine is present in the Aplysia nervous system in concentrations similar to that of octopamine. These are receptors that are very specific for phenylethanolamine, which on different neurons mediate sodium, chlorine, or potassium conductance increase responses. These observations indicate that phenylethanolamine may act as a neurotransmitter in Aplysia.

Thyrotropin-releasing hormone in specific nuclei of rat brain.

The regional distribution of thyrotropin-releasing hormone (TRH) in rat brain was studied. The greatest concentration of TRH was found in the median eminence. High concentrations were also found in several hypothalamic nuclei. Outside the hypothalamus, relatively large amounts of TRH were found in the septal and preoptic areas.

Octopamine: presence in single neurons of Aplysia suggests neurotransmitter function.

Octopamine has been identified and measured in individual neurons from Aplysia californica. Neither dopamine nor norepinephrine was detected in these cells. Thus, in Aplysia there may be separate populations of catecholaminergic and monophenolaminergic cells. Octopamine may have functions of its own in the central nervous system of mollusks.

Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances.

Fibromyalgia (FM) is characterised by chronic widespread pain and allodynia (pain from stimuli which are not normally painful with pain that may occur other than in the area stimulated) of more than 3 months duration. The current hypothesis of the aetiology of FM includes inflammatory and neuroendocrine disorders. The biophysiology of this syndrome, however; remains still widely elusive, and there are no formally approved therapies. Non-pharmacological interventions in FM patients include habitual exercise programs which improve physical function and quality of life of patients and may even reduce pain. However the mechanisms through which exercise benefits FM symptoms needs to be elucidated. In this article we firstly review the main topics and characteristics of the FM syndrome, while focusing our attention on the inflammatory hypothesis of FM, as well as on the beneficial effects of habitual exercise as a co-therapy for FM patients. In this context, the latest developments in research on anti-inflammatory effects of exercise are also reviewed and discussed. To find out what is known about the connection between benefits of exercise for FM and anti-inflammatory effects of exercise, we carried out a PubMed search using the term "fibromyalgia" and "exercise" together with "inflammation", and no more than ten published articles were found (six of them reviews), which are also discussed. In the second part of the article we present a pilot investigation on a group of 14 female FM patients with a diagnosis of FM by a rheumatologist. They took part in a pool-aquatic program in warm water over a period of fourth months (three weekly 60-min sessions). Circulating inflammatory (IL-1beta, IL-2, IFNgamma, TNFalpha, IL-8, IL-6, IL-4, IL-10 and CRP) and neuroendocrine (NA and cortisol) markers were determined. FM patients showed higher circulating levels of IL-8, IFNgamma and CRP as well as cortisol and NA than age-matched healthy control women. After the exercise program, a significant decrease in IL-8, IFNgamma, and CRP were found, in parallel with a decrease in circulating concentrations of cortisol and increased levels of NA. The results confirm an elevated "inflammatory status" in the FM syndrome and strengthen the hypothesis that the benefits of exercise in FM patients are mediated, at least in part, by its anti-inflammatory effects. A better regulation of the cytokine-HPA axis feedback may be also involved.

In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving the testicular renin-angiotensin system.

Men are at greater risk of cardiovascular and renal diseases than women. Several hypertensive rat models also exhibit gender differences in blood pressure. Although the mechanisms responsible for these gender differences are not clear, androgens have been shown to promote hypertension. Testosterone is produced by Leydig cells under the regulation of catecholamines acting through both alpha- and beta-adrenoceptors. Some investigators have postulated a putative role of angiotensin II (Ang II) in modulating the action of gonadotropin in Leydig cells, inhibiting testosterone production. In the present work, we analysed the potential mechanism by which the testicular renin-angiotensin system (RAS) decreases the serum circulating levels of testosterone after the in vivo administration of the long-acting selective alpha(1)-adrenergic receptor antagonist doxazosin. RAS was analysed through assessment of the activity of its proteolytic regulatory enzymes. We can conclude that the testicular testosterone production, at least in rat, is regulated by catecholamines through a mechanism involving alpha(1)-adrenergic receptors and RAS, with a putative role for Ang III. Because doxazosin is usually used as a pharmacological therapy in the treatment of hypertension and benign prostatic hyperplasia, our results could also indicate that its benefits are due, at least in part, to decreased serum circulating levels of testosterone.

Angiotensin II AT(1) receptor blockade selectively enhances brain AT(2) receptor expression, and abolishes the cold-restraint stress-induced increase in tyrosine hydroxylase mRNA in the locus coeruleus of spontaneously hypertensive rats.

Spontaneously hypertensive rats, a stress-sensitive strain, were pretreated orally for 14 days with the AT(1) receptor antagonist candesartan before submission to 2 h of cold-restraint stress. In non-treated rats, stress decreased AT(1) receptor binding in the median eminence and basolateral amygdala, increased AT(2) receptor binding in the medial subnucleus of the inferior olive, decreased AT(2) binding in the ventrolateral thalamic nucleus and increased tyrosine hydroxylase mRNA level in the locus coeruleus. In non-stressed rats, AT(1) receptor blockade reduced AT(1) receptor binding in all areas studied and enhanced AT(2) receptor binding in the medial subnucleus of the inferior olive. Candesartan pretreatment produced a similar decrease in brain AT(1) binding after stress, and prevented the stress-induced AT(2) receptor binding decrease in the ventrolateral thalamic nucleus. In the locus coeruleus and adrenal medulla, AT(1) blockade abolished the stress-induced increase in tyrosine hydroxylase mRNA level. Our results demonstrate that oral administration of candesartan effectively blocked brain AT(1) receptors, selectively increased central AT(2) receptor expression and prevented the stress-induced central stimulation of tyrosine hydroxylase transcription. The present results support a role of brain AT(1) and AT(2) receptors in the regulation of the stress response, and the hypothesis that AT(1) receptor antagonists may be considered as potential therapeutic compounds in stress related disorders in addition to their anti-hypertensive properties.

Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Angiotensin II is a vasoactive peptide and may act as a growth factor in vascular smooth muscle cells. Experimental injury of the rat aorta causes rapid migration of medial smooth muscle cells and their proliferation resulting in the formation of neointima. We have examined, using quantitative autoradiography, the expression of angiotensin II receptor subtypes AT1 and AT2, and angiotensin-converting enzyme, in the neointima formed in the rat thoracic aorta 15 d after balloon-catheter injury. In contrast to the normal aortic wall, which contained both AT1 and AT2 receptors (80% and 20%, respectively), neointimal cells expressed almost exclusively angiotensin II AT1 receptors. The apparent number of these receptors was fourfold higher in the neointima compared to that in the normal aortic wall. The affinities of the neointimal receptors to angiotensin II or to the AT1 receptor antagonist, losartan, were not different from those in the normal aortic wall. Angiotensin-converting enzyme binding in the neointima was not different from that in the media of the uninjured aorta. Our data suggest that angiotensin II AT1 receptors may have a significant role in injury-induced vascular smooth muscle proliferation and migration.

Modelling diseases: the allergens of Olea europaea pollen.

This study analyzes the influence of the IgE response to certain olive pollen allergens in the modulation of the different clinical phenotypes of allergic disease and their relationship with the level of exposure to pollen and genetic factors. Patients from high-exposure areas had a complex IgE antibody response to allergens of Olea euroapea, which included 3 or more allergens in 75% of cases. The majority allergens were Ole e 1, Ole e 2 (profilin), Ole e 7 (lipid transporting protein), Ole e 9 (glucanase), and Ole e 10. The existence of the antigen HLA-DR2 (15) led to a higher risk of sensitization to Ole e 10 and a greater trend towards the development of severe asthma, which increased in the presence of an anti-profilin IgE. Thirty percent of patients suffering from pollinosis simultaneously presented allergy to vegetable foods. Anti-Ole e 7 IgE was significantly associated with fruit anaphylaxis and anti-profilin IgE was detected in 90% of patients with oral syndrome. Finally, we analyzed the role of glucanase and Ole e 10 as causes of the pollen-latex-fruit syndrome.

Influence of a medium-impact aquaerobic program on health-related quality of life and fitness level in healthy adult females.

AIM: The aim of the study was to examine the influence of a medium-impact aquaerobic program on the health-related quality of life (HRQoL) and health-related fitness (HRF) level of middle-aged healthy female subjects. METHODS: Twenty apparently healthy women (mean age: 43.1 [standard deviation: 9.7] years) participated in the study. Criteria for inclusion were absence of diagnosed illnesses, as well and signs and symptoms of disease as evaluated by the Physical Activity Readiness Questionnaire. Participants carried out a medium-impact aquaerobic exercise program consisting of 2 weekly sessions of 60 min during 8 months. Before and after the exercise program, HRQoL was assessed by the 36-item short form health survey (SF-36) questionnaire, and HRF was measured using a simplified version of the AFISAL-INEFC HRF test battery. RESULTS: Following the exercise program, an increase in all domains of HRQoL, except general health and role-emotional, was observed. Total body mass and body fat percentage decreased, and estimated aerobic power increased. CONCLUSION: Completion of a medium-impact aquaerobic program (2 weekly sessions of 60 min during 8 months) improves HRQoL in most domains, particularly bodily pain and vitality, and shows to be among the most effective programs for improving perceived quality of life. Moreover, this exercise program proved to have a positive influence on the body composition and functional capacity of the subjects, being effective in reducing fat body mass and improving cardiorespiratory function.

Reallocating sedentary time to moderate-to-vigorous physical activity but not to light-intensity physical activity is effective to reduce adiposity among youths: a systematic review and meta-analysis.

The aim of the study was to summarize the evidence of the effects of reallocating time spent in sedentary behaviours in different activity intensities on youth's adiposity. Five databases were searched. Studies that reported the effects of replacing sedentary behaviour with light-intensity physical activity (LIPA) and/or moderate-to-vigorous physical activity (MVPA) on at least one adiposity parameter. The estimated regression coefficients (ß) and 95% CIs were combined and meta-analysed. Data from 7,351 youths and five studies were analysed. Pooled analysis from cross-sectional studies shows that replacing sedentary time with LIPA showed no significant associations with any adiposity-related outcomes. Replacing sedentary time with MVPA was statistically associated with total body fat percentage (ß = -2.512; p = 0.003), but not with body mass index or waist circumference. In subgroup analysis, the greatest magnitude of association was observed from studies where 60 min of sedentary behaviour was reallocated to 60 min of MVPA (ß = -4.535; p < 0.001). Our results highlight the importance of promoting MVPA, which may improve body composition phenotypes in young people. This information can be used to develop more effective lifestyle interventions.

Is high-intensity interval training more effective on improving cardiometabolic risk and aerobic capacity than other forms of exercise in overweight and obese youth? A meta-analysis.

BACKGROUND: The scientific interest in high-intensity interval training (HIIT) has greatly increased during recent years. OBJECTIVE: The objective of this meta-analysis was to determine the effectiveness of HIIT interventions on cardio-metabolic risk factors and aerobic capacity in overweight and obese youth, in comparison with other forms of exercise. DATA SOURCES: A computerized search was made using seven databases. STUDY ELIGIBILITY CRITERIA: The analysis was restricted to studies that examined the effect of HIIT interventions on cardio-metabolic and/or aerobic capacity in pediatric obesity (6-17 years old). PARTICIPANTS AND INTERVENTIONS: Nine studies using HIIT interventions were selected (n = 274). STUDY APPRAISAL AND SYNTHESIS METHODS: Standarized mean difference (SMD) and 95% confidence intervals were calculated. The DerSimonian-Laird approach was used. RESULTS: HIIT interventions (4-12 week duration) produced larger decreases in systolic blood pressure (SMD = 0.39; -3.63 mmHg) and greater increases in maximum oxygen uptake (SMD = 0.59; 1.92 ml/kg/min) than other forms of exercise. Also, type of comparison exercise group and duration of study were moderators. CONCLUSIONS: HIIT could be considered a more effective and time-efficient intervention for improving blood pressure and aerobic capacity levels in obese youth in comparison to other types of exercise. © 2016 World Obesity.