Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom

The biological activity of the proline rich decapeptde Bj PRO 10c a processing product of the C type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensm converting enzyme activity with subsequent ant hypertensive effect However recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide Here we show that Bj PRO 10c enhances and sustains the generation of nitric made (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline NO cycle Bj PRO 10c-mediated effects not restricted to the cardiovascular system since NO production was also induced in cells of astroglial origin Bj PRO 10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline NO cycle cells in a dose dependent fashion In view of that, astroglial cells function as L arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS Moreover, proliferation of astroglial cells was reduced in the presence of Bj PRO 10c however, cell death was not induced Since NO donors have been studied for the treatment of solid cancers Bj PRO 10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide`s ability to augment NO production (C) 2010 Elsevier B V All rights reserved

O-GlcNAcylation Contributes to Augmented Vascular Reactivity Induced by Endothelin 1

O-GlcNAcylation augments vascular contractile responses, and O-GlcNAc-proteins are increased in the vasculature of deoxycorticosterone-acetate salt rats. Because endothelin 1 (ET-1) plays a major role in vascular dysfunction associated with salt-sensitive forms of hypertension, we hypothesized that ET-1-induced changes in vascular contractile responses are mediated by O-GlcNAc modification of proteins. Incubation of rat aortas with ET-1 (0.1 mu mol/L) produced a time-dependent increase in O-GlcNAc levels and decreased expression of O-GlcNAc transferase and beta-N-acetylglucosaminidase, key enzymes in the O-GlcNAcylation process. Overnight treatment of aortas with ET-1 increased phenylephrine vasoconstriction (maximal effect [in moles]: 19 +/- 5 versus 11 +/- 2 vehicle). ET-1 effects were not observed when vessels were previously instilled with anti-O-GlcNAc transferase antibody or after incubation with an O-GlcNAc transferase inhibitor (3-[2-adamantanylethyl]-2-[{4-chlorophenyl}azamethylene]-4-oxo-1,3-thiazaperhyd roine-6-carboxylic acid; 100 mu mol/L). Aortas from deoxycorticosterone-acetate salt rats, which exhibit increased prepro-ET-1, displayed increased contractions to phenylephrine and augmented levels of O-GlcNAc proteins. Treatment of deoxycorticosterone-acetate salt rats with an endothelin A antagonist abrogated augmented vascular levels of O-GlcNAc and prevented increased phenylephrine vasoconstriction. Aortas from rats chronically infused with low doses of ET-1 (2 pmol/kg per minute) exhibited increased O-GlcNAc proteins and enhanced phenylephrine responses (maximal effect [in moles]: 18 +/- 2 versus 10 +/- 3 control). These changes are similar to those induced by O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate, an inhibitor of beta-N-acetylglucosaminidase. Systolic blood pressure (in millimeters of mercury) was similar between control and ET-1-infused rats (117 +/- 3 versus 123 +/- 4 mm Hg; respectively). We conclude that ET-1 indeed augments O-GlcNAc levels and that this modification contributes to the vascular changes induced by this peptide. Increased vascular O-GlcNAcylation by ET-1 may represent a mechanism for hypertension-associated vascular dysfunction or other pathological conditions associated with increased levels of ET-1. (Hypertension. 2010; 55: 180-188.)

Black-box decomposition approach for computational hemodynamics: One-dimensional models

Increasing efforts exist in integrating different levels of detail in models of the cardiovascular system. For instance, one-dimensional representations are employed to model the systemic circulation. In this context, effective and black-box-type decomposition strategies for one-dimensional networks are needed, so as to: (i) employ domain decomposition strategies for large systemic models (1D-1D coupling) and (ii) provide the conceptual basis for dimensionally-heterogeneous representations (1D-3D coupling, among various possibilities). The strategy proposed in this article works for both of these two scenarios, though the several applications shown to illustrate its performance focus on the 1D-1D coupling case. A one-dimensional network is decomposed in such a way that each coupling point connects two (and not more) of the sub-networks. At each of the M connection points two unknowns are defined: the flow rate and pressure. These 2M unknowns are determined by 2M equations, since each sub-network provides one (non-linear) equation per coupling point. It is shown how to build the 2M x 2M non-linear system with arbitrary and independent choice of boundary conditions for each of the sub-networks. The idea is then to solve this non-linear system until convergence, which guarantees strong coupling of the complete network. In other words, if the non-linear solver converges at each time step, the solution coincides with what would be obtained by monolithically modeling the whole network. The decomposition thus imposes no stability restriction on the choice of the time step size. Effective iterative strategies for the non-linear system that preserve the black-box character of the decomposition are then explored. Several variants of matrix-free Broyden`s and Newton-GMRES algorithms are assessed as numerical solvers by comparing their performance on sub-critical wave propagation problems which range from academic test cases to realistic cardiovascular applications. A specific variant of Broyden`s algorithm is identified and recommended on the basis of its computer cost and reliability. (C) 2010 Elsevier B.V. All rights reserved.

Eficácia do treinamento de força sobre parâmetros cardiovasculares e antropométricos em adultos sedentários

This study aimed to determine the influence of strength training (ST), in three weekly sessions over ten weeks, on cardiovascular parameters and anthropometric measurements. It is a before and after intervention trial, with a sample composed of 30 individuals. Participants were adults aged between 18 and 40 years, from both sexes and sedentary for at least three months previously. Tests were computed ergospirometry, CRP, PWV and body composition (dependent variables) before and after the experiment. Independent variables, age and sex, were considered in order to determine their influence on the dependent variablesevaluatedend. By comparing the initial cardiovascular parameters with those obtained after intervention in patients undergoing the ST proposed (a Student s t-test was conducted within each group for samples matched to parameters with normal distribution, while the Wilcoxin was applied for those without), there was no significant difference in PWV(p =0469) or PCR(p =0.247), but there was an increase in anaerobic threshold(AT) (p=0.004) and Maximal Oxygen Uptake(VO2max) (p =0.052). In regard to anthropometric measures, individuals significantly reduced their body fat percentage (p<0.001) and fat mass (p<0,001), as well as increasing lean mass (p<0.001). However, no changes were recorded in the waist-to-hip ratio (WHR) (p= 0.777), body mass (p=0.226) or body mass index (BMI) (p =0.212). Findings of this study lead us to believe that the proposed ST, and did not increase the VOP or PCR improves cardiorespiratory capacity and body composition. Devotees of this training can therefore safely enjoy all its benefits without risk to the cardiovascular system

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da capacidade de caminhar do portador de obesidade mórbida utilizando teste de caminhada de 6 minutos

Introduction: The ability to walk is impaired in obese by anthropometric factors (BMI and height), musculoskeletal pain and level of inactivity. Little is known about the influence of body adiposity and the acute response of the cardiovascular system during whole the 6-minute walk test (6mWT). Objective: To evaluate the effect of anthropometric measures (BMI and WHR waist-to-hip ratio), the effort heart and inactivity in ability to walk the morbidly obese. Materials and Methods: a total 36 morbidly obese (36.23 + 11.82 years old, BMI 49.16 kg/m2) were recruited from outpatient department of treatment of obesity and bariatric surgery in University Hospital Onofre Lopes and anthropometric measurements of obesity (BMI and WHR), pulmonary function, pattern habitual physical activity (Baecke Questionnaire) and walking capacity (6mWT). The patient was checking to measure: heart rate (HR), breathing frequency (BF), peripheral oxygen saturation, level of perceived exertion, systemic arterial pressure and duplo-produto (DP), moreover the average speed development and total distance walking. The data were analysed between gender and pattern of body adiposity, measuring the behavior minute by minute of walking. The Pearson and Spearmam correlation coefficients were calculated, and stepwise multiple Regression examined the predictors of walking capacity. All analyses were performed en software Statistic 6.0. Results: 20 obese patients had abdominal adiposity (WHR = 1.01), waist circumference was 135.8 cm in women (25) and 139.8 cm in men (10). Walked to the end of 6mWT 412.43 m, with no differences between gender and adiposity. The total distance walked by obesity alone was explained by BMI (45%), HR in the sixth minute (43%), the Baecke (24%) and fatigue (-23%). 88.6% of obese (31) performed the test above 60% of maximal HR, while the peak HR achieved at 5-minute of 6mWT. Systemic arterial pressure and DP rised after walking, but with no differences between gender and adiposity. Conclusion: The walk of obese didn´t suffers influence of gender or the pattern of body adiposity. The final distance walked is attributed to excess body weight, stress heart, the feeling of effort required by physical activity and level of sedentary to obese. With a minute of walking, the obeses achieved a range of intensity cardiovascular trainning

Prevalência de doença arterial obstrutiva periférica (DAOP) e alterações sensoriais em pacientes diabéticos tipo 2: impacto da DAOP sobre a qualidade de vida, nível de atividade física e composição corporal

Diabetes Mellitus (DM) affected approximately 171 million people in the world in the year 2000 as described by the World Health Organization (WHO). Because DM is a multisystem disease it can cause several complications especially those related to the cardiovascular system. The Peripheral Arterial Disease (PAD) of the lower limbs and the Diabetic Distal Symmetric Polyneuropathy (DDSP) can affect the DM patient causing consequences as the diabetic foot and eventually amputations. The main objective of this study was to determine the prevalence of PAD and sensorial impairment in 73 type 2 DM (DM2) patients and also assess the impact of PAD on quality of life, level of physical activity and body composition. For clinical assessment it was used: the ankle-brachial index (ABI); quantitative sensorial test for tactile sensibility (ST), pain (SD), vibration (SV); Achilles tendon reflex (RA); quality of life questionnaire (SF-36); modified Baecke physical activity questionnaire and bioelectric impedance. Prevalence of PAD in the studied population was 13.7%. ABI was inversely correlated to age (p=0,03; rhô= -0,26), diabetes duration (p=0,02; rhô= -0,28) and blood pressure (p= 0,0007; rhô= -0,33). There were lower scores for physical health summary on the SF-36 in DM2 patients; however, the presence of PAD predominantly mild did not significantly impact quality of life, body composition or physical activity level assessed by questionnaire. Fourteen patients (19.2%) present bilateral and symmetrical alterations in two or more sensorial tests compatible to DPN diagnosis. Abnormalities in ST, SD and SV were present in 27.3%, 24.6% and 8.2%; respectively. There was association of results from ST abnormalities with RA and mainly with SD, suggesting the importance of 10g monofilament use in DM2 routine assessment. In conclusion, the prevalence of PAD in subclinical DM2 was slightly higher compared to the general population and in agreement to previously published data in DM patients. The PAD severity was predominantly mild and still without repercussion on quality of life and body composition. Our study demonstrated a significant prevalence of both PAD and DPN in DM2 without previous diagnosis of these complications and indicates the necessity of early preventive and therapeutic interventions for this population

Comparação das respostas fisiológicas entre diferentes testes funcionais em obesos

obesity affects rightly functional capacity diminishing the cardiovascular system efficiency and oxygen uptake (VO2). Field tests, such as, Incremental Shuttle Walking Test (ISWT) and Six Minute Walk Test (6MWT) has been employed as alternative of Cardiopulmonary Exercise Test (CPX), to functional assessing for conditions which transport of oxygen to peripheral is diminished. Nevertheless, the knowing about metabolic variables response in real time and it comparing among different maximal and submaximal tests in obese is absent. Aim: to compare cardiopulmonary, metabolic response during CPX, ISWT and 6MWT and to analyse it influence of adiposity markers in obese. Material e Method: crosssectional, prospective study. Obese included if: (BMI>30Kg/m2; FVC>80%), were assessed as clinical, anthropometric (BMI, body adiposity index-BAI, waist-WC, hip- HC and neck-NC circumferences) and spirometry (forced vital capacity-FVC, Forced expiratory volume-1°second-FEV1, maximal voluntary ventilation-MVV) variables. Obese performed the sequence of tests: CPX, ISWT and 6MWT. Throughout tests was assessed breath-by-breath by telemetry system (Cortex-Biophysik-Metamax3B) variables; oxygen uptake on peak of activity (VO2peak); carbon dioxide production (VCO2); Volume Expiratory (VE); ventilatory equivalents for VO2 (VE/VO2) and CO2 (VE/VCO2); respiratory exchange rate (RER) and perceived effort-Borg6-20). Results: 15 obese (10women) 39.4+10.1years, normal spirometry (%CVF=93.7+9.7) finished all test. They have BMI (43.5+6.6kg/m2) and different as %adiposity (BAI=50.0+10.5% and 48.8+16.9% respectively women and men). Difference of VO2ml/kg/min and %VO2 were finding between CPX (18.6+4.0) and 6MWT (13.2+2.5) but not between ISWT (15.4+2.9). Agreement was found for ISWT and CPX on VO2Peak (3.2ml/kg/min; 95%; IC-3.0 9.4) and %VO2 (16.4%). VCO2(l/min) confirms similarity in production for CPX (2.3+1.0) and ISWT (1.7+0.7) and difference for 6MWT (1.4+0.6). WC explains more the response of CPX and ISWT than other adiposity markers. Adiposity diminishes 3.2% duration of CPX. Conclusion: ISWT promotes similar metabolic and cardiovascular response than CPX in obese. It suggesting that ISWT could be useful and reliable to assess oxygen uptake and functional capacity in obese

Auditory stimulation and cardiac autonomic regulation

Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: auditory stimulation, autonomic nervous system, music and heart rate variability. The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.

O treinamento nos valores da V200, FCpico e distância percorrida de cavalos da raça Árabe e Crioula

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Perinatal lead exposure affects nitric oxide and cyclooxygenase pathways in aorta of weaned rats

Perinatal Pb exposure may modulate arterial tone through nitric oxide (NO) and cyclooxygenase products. To investigate this, Wistar dams received 1000 ppm of Pb or sodium acetate (control) in drinking water during pregnancy and lactation. Curves were constructed in phenylephrine-precontracted intact and/or denuded rings of thoracic aortas of weaned (23-day-old) male pups from their responses to N-omega-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and ACh in the absence or presence of indomethacin (10(-5)M, cyclooxygenase inhibitor) or L-NAME (3 x 10(-7)M and 3 x 10(-4)M). Blood lead concentration and systolic blood pressure (SBP) were higher in intoxicated than control pups (blood lead mu g/dl: control < 3.0, Pb 58.7 +/- 6.5*; SBP mmHg: control 111.4 +/- 2.3, Pb 135.5 +/- 2.4*). In L-NAME-treated rings maximal responses increased in Pb-exposed rats, and were higher in intact than in denuded aortas (contraction [% of phenylephrine] intact: control 184.3 +/- 23.7, Pb 289.1 +/- 18.3*; denuded: control 125.1 +/- 4.5, Pb 154.8 +/- 13.3*). ACh-induced relaxation in intact aortas from Pb-exposed rats presented rightward shift in L-NAME presence (EC50 x 10(-7)M: control 1.32 [0.33-5.18], Pb 4.88 [3.56-6.69]*) but moved left under indomethacin (EC50 x 10(-7)M: control 8.95 [3.47-23.07], Pb 0.97 [0.38-2.43]*). *p < 0.05 significant relative to the respective control; N = 7-9. Endothelium removal abolished ACh-induced relaxation. Perinatal Pb exposure caused hypertension associated with alterations in the production and/or release of basal and stimulated endothelium-derived relaxing factors-NO and constricting cyclooxygenase products. These findings may help explain the contribution of NO and cyclooxygenase products to the etiology and/or maintenance of Pb-induced hypertension and could ultimately lead to therapeutic advantages in plumbism.

Beneficial Effects of Physical Training on the Cardio-Inflammatory Disorder Induced by Lung Ischemia/Reperfusion in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Phylogeny, Ecology, and Heart Position in Snakes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The unequal influences of the left and right vagi on the control of the heart and pulmonary artery in the rattlesnake, Crotalus durissus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Exercício físico, receptores β-adrenérgicos e resposta vascular

O exercício aeróbio promove efeitos benéficos na prevenção e tratamento de doenças como hipertensão arterial, aterosclerose, insuficiência venosa e doença arterial periférica. Os receptores β-adrenérgicos estão presentes em várias células. No sistema cardiovascular, promovem inotropismo e cronotropismo positivo cardíaco e relaxamento vascular. Embora os efeitos do exercício tenham sido investigados em receptores cardíacos, estudos focados nos vasos são escassos e controversos. Esta revisão abordará os efeitos do exercício físico sobre os receptores β-adrenérgicos vasculares em modelos animais e humanos e os mecanismos celulares envolvidos na resposta relaxante. em geral, os estudos mostram resultantes conflitantes, onde observam diminuição, aumento ou nenhum efeito do exercício físico sobre a resposta relaxante. Assim, os efeitos do exercício na sensibilidade β-adrenérgica vascular merecem maior atenção, e os resultados mostram que a área de fisiopatologia vascular é um campo aberto para a descoberta de novos compostos e avanços na prática clínica.