Effectiveness of short sprint interval training in women with major depressive disorder: a proof-of-concept study.

Background: High-intensity intermittent training has emerged as an option for treating major depressive disorder (MDD). However, short sprint training (sSIT), an efficient HIIT modality, has not been tested yet for this purpose. The sSIT has been proven to induce the same metabolic adaptations, with the advantage of promoting lower muscle fatigue than other HIIT protocols. Methods: Seventeen adult women diagnosed with moderate/severe MDD were randomly allocated into a sSIT group (n=9) or a control condition (n=8). The sSIT group completed, over two weeks, six 6-10-min sessions which consisted of 3-12 "all out" sprints of 5 s interspersed with low-intensity recovery of 30-45 s. The week before and after the intervention, both groups were evaluated with the Hamilton Depression Rating Scale of 21-itens (HAM-D21), and for physical fitness and incidental physical activity. Results: The sSIT group exhibited significant improvements for HAM-D21 scores (24.6±8.2 vs. 16.8±10.1), maximum aerobic power (140±15 vs. 155±15 W), countermovement jump (13.0±3.4 vs. 14.9±3.1 cm), % of body fatness (32.4±4.4 vs. 29.3±3.8%), and 4-days number of steps (13,626±11,309 vs. 16,643±15,371) after the training period when compared to the control group. Conclusion: Less than 1 hour of a sSIT protocol over two weeks have demonstrated to reduce depressive symptoms, while improving aerobic fitness and body composition, and increasing incidental physical activity in a sample of women diagnosed with MDD.

Efficacy of Different Cold-Water Immersion Temperatures on Neuromotor Performance in Young Athletes.

Cold-Water-Immersion (CWI) has been frequently used to accelerate muscle recovery and to improve performance after fatigue onset. In the present study, the aim was to investigate the effects of different CWI temperatures on neuromuscular activity on quadriceps after acute fatigue protocol. Thirty-six young athletes (16.9 ± 1.4 years-old; 72.1 ± 13.8 kg; 178.4 ± 7.2 cm) were divided into three groups: passive recovery group (PRG); CWI at 5 °C group (5G); and CWI at 10 °C group (10G). All participants performed a fatigue exercise protocol; afterwards, PRG performed a passive recovery (rest), while 5G and 10G were submitted to CWI by means of 5 °C and 10 °C temperatures during 10 min, respectively. Fatigue protocol was performed by knee extension at 40% of isometric peak force from maximal isometric voluntary contraction. Electromyography was used to evaluate neuromuscular performance. The passive recovery and CWI at 5 °C were associated with normalized isometric force and quadriceps activation amplitude from 15 until 120 min after exercise-induced fatigue (F = 7.169, p < 0.001). CWI at 5 °C and 10 °C showed higher muscle activation (F = 6.850, p < 0.001) and lower median frequency (MF) than passive recovery after 15 and 30 min of fatigue (F = 5.386, p < 0.001). For neuromuscular efficiency (NME) recovery, while PRG normalized NME values after 15 min, 5G and 10G exhibited these responses after 60 and 30 min (F = 4.330, p < 0.01), respectively. Passive recovery and CWI at 5 °C and 10 °C revealed similar effects in terms of recovery of muscle strength and NME, but ice interventions resulted in higher quadriceps activation recovery.

Effects of Circuit Weight-Interval Training on Physical Fitness, Cardiac Autonomic Control, and Quality of Life in Sedentary Workers.

Sedentary behaviors, those that involve sitting and low levels of energy expenditure, have been associated with several adverse cardiometabolic effects. This study evaluated the chronic effects of a combined circuit weight interval training (CWIT) on physical fitness, quality of life, and heart rate variability (HRV), and compared the effects of CWIT-induced autonomic adaptations on different postures in adult sedentary workers. Twenty-seven sedentary workers (age 36.9 ± 9.2 years old, 13 men and 14 women) were divided into two groups: control, who continued their sedentary behavior, and experimental, who were submitted to a CWIT for 12 weeks, completing two ~40 min sessions per week. Monitoring of 8th, 16th, and 24th sessions revealed a moderate training load during sessions. Participants exhibited an improved aerobic capacity (VO2max, 34.03 ± 5.36 vs. 36.45 ± 6.05 mL/kg/min, p < 0.05) and flexibility (22.6 ± 11.4 vs. 25.3 ± 10.1 cm, p < 0.05) after the training period. In addition, they showed greater quality of life scores. However, the CWIT did not change body composition. Interestingly, more HRV parameters were improved in the seated position. The CWIT used in the current study was associated with improvements in several fitness and quality of life parameters, as well as in cardiac autonomic control of HR in adult sedentary workers. Examination of different body positions when evaluating changes in HRV appears to be a relevant aspect to be considered in further studies. Future randomized controlled trials (RCTs) with larger samples of both sexes should confirm these promising results.

Influence of high-intensity interval training and intermittent fasting on myocardium apoptosis pathway and cardiac morphology of healthy rats.

AIM: To evaluate the influence of intermittent fasting and high-intensity interval training (HIIT) on myocardial apoptosis signaling and cardiac morphological characteristics in healthy rats. METHODS: Male Wistar rats (n = 60) were divided into four groups: sedentary control (SED-C), intermittent fasting (SED-IF), high-intensity interval training (HIIT-C), and high-intensity interval training plus intermittent fasting (HIIT-IF). SED-C and HIIT-C groups were treated daily with ad libitum chow; SED-IF and HIIT-IF received the same standard chow every other day. HIIT-C and HIIT-IF rats were submitted to an HIIT protocol five times a week for 12 weeks. At the end of the experiment, functional capacity, cardiac morphology, and expression of apoptosis signaling pathways-related proteins were analyzed. KEY FINDINGS: HIIT increased cardiomyocyte cross-sectional area, collagen interstitial fraction, and the pro-apoptotic proteins AIF and caspase-3 expression, and reduced pro-apoptotic protein CYTC expression and the cleaved-to-non-cleaved PARP-1 ratio in myocardium. Intermittent fasting reduced cardiomyocyte cross-sectional area, collagen interstitial fraction, and expression of Bax, CYTC and cleaved PARP-1, and increased expression of the anti-apoptotic protein BCL-2. SMAC, ARC, and caspase-8 expression was not changed by HIIT or intermittent fasting. SIGNIFICANCE: HIIT promotes cardiomyocyte hypertrophy and interstitial fibrosis, and modulates the apoptosis signaling pathway in healthy rat myocardium. Intermittent fasting reduces pro-apoptotic and increases antiapoptotic signaling, besides attenuating HIIT-induced cardiomyocyte hypertrophy and myocardial interstitial fibrosis.

Effects of AT1 receptor antagonism on interstitial and ultrastructural remodeling of heart in response to a hypercaloric diet.

Palatable hypercaloric feeding has been associated with angiotensin-II type 1 receptor (AT1R) stimulation and cardiac remodeling. This study analyzed whether AT1R antagonism attenuates cardiac remodeling in rats subjected to a palatable hypercaloric diet. Male Wistar-Kyoto rats were subjected to a commercial standard rat chow (CD) or a palatable hypercaloric diet (HD) for 35 weeks and then allocated into four groups: CD, CL, HD, and HL; L groups received losartan in drinking water (30 mg/kg/day) for 5 weeks. Body weight, adiposity, and glycemia were evaluated. The cardiovascular study included echocardiography, and myocardial morphometric and ultrastructural evaluation. Myocardial collagen isoforms Type I and III were analyzed by Western blot. Both HD and HL had higher adiposity than their respective controls. Cardiomyocyte cross-sectional-area (CD 285 ± 49; HD 344 ± 91; CL 327 ± 49; HL 303 ± 49 µm2 ) and interstitial collagen fractional area were significantly higher in HD than CD and unchanged by losartan. HD showed marked ultrastructural alterations such as myofilament loss, and severe mitochondrial swelling. CL presented higher Type I collagen expression when compared to CD and HL groups. The ultrastructural changes and type I collagen expression were attenuated by losartan in HL. Losartan attenuates systolic dysfunction and ultrastructural abnormalities without changing myocardial interstitial remodeling in rats subjected to a palatable hypercaloric diet.

Autonomic modulations of heart rate variability are associated with sports injury incidence in sprint swimmers.

OBJECTIVES: Young athletes' participation in competitive sports is becoming increasingly common, and this increased involvement raises concerns about the occurrence of overtraining and sports injuries. Since these issues are poorly understood, this study analyzed heart rate variability, stress/recovery relationship, and sports injury incidence during a training macrocycle of young sprint and endurance swimmers. METHODS: Thirty teenage swimmers (aged 12 to 17 years) were divided into two groups as follows: Sprint (n = 17) and Endurance (n = 13). Subjects were evaluated over 20 weeks, based on the following three schedules: general, specific, and competitive. In addition to heart rate variability and sports injury incidence, the Recovery-Stress-Questionnaire of Athletes was used to analyse stress/recovery states in athletes. All procedures were developed at the initial moment and at the end of each periodization step. RESULTS: The Sprint group presented a reduced standard deviation of normal-normal beats (73.0 ± 6.6 vs. 54.1 ± 3.5 ms; p < 0.05) and root mean square of the successive differences (55.3 ± 6.2 vs. 42.0 ± 3.7 ms; p < 0.01) from the period of general preparation until the time of competition. Recovery-stress monitoring was affected only by the swimming training periodization (p < 0.05). During the general period, differences between recovery and stress scales were correlated directly with the root mean square of the successive differences (r = 0.576; p = 0.001), the standard deviation of instantaneous variability beat-to-beat (r = 0.521; p = 0.003) and the triangular index (r = 0.476; p = 0.008). Differences between general recovery and stress scales were inversely correlated with geometric indexes after the specific training period. Moreover, the Sprint group showed a higher incidence of sports injury than the Endurance group (0.0214 ± 0.0068 vs. 0.0136 ± 0.0050 cases/1000 hours). CONCLUSION: Sprint training was associated with progressive activation of the sympathetic nervous system as well as a higher incidence of sports injury in comparison to endurance swimming during a training macrocycle.

Association between echocardiographic structural parameters and body weight in Wistar rats.

BACKGROUND: The association between echocardiographic structural parameters and body weight (BW) during rat development has been poorly addressed. We evaluated echocardiographic variables: left ventricular (LV) end-diastolic (LVDD) and end-systolic (LVSD) diameters, LV diastolic posterior wall thickness (PWT), left atrial diameter (LA), and aortic diameter (AO) in function of BW during development.Results/Materials and Methods: Male Wistar rats (n = 328, BW: 302-702 g) were retrospectively used to construct regression models and 95% confidence intervals relating to cardiac structural parameters and BW. Adjusted indexes were significant to all relationships; the regression model for predicting LVDD (R2 = 0.678; p < 0.001) and AO (R2 = 0.567; p < 0.001) had the highest prediction coefficients and LA function the lowest prediction coefficient (R2 = 0.274; p < 0.01). These relationships underwent validation by performing echocardiograms on additional rats (n = 43, BW: 300-600 g) and testing whether results were within confidence intervals of our regressions. Prediction models for AO and LA correctly allocated 38 (88.4%) and 39 rats (90.7%), respectively, within the 95% confidence intervals. Regression models for LVDD, LVSD, and PWT included 27 (62.7%), 30 (69.8%), and 19 (44.2%) animals, respectively, within the 95% confidence intervals. CONCLUSIONS: Increase in cardiac structures is associated with BW gain during rat growth. LA and AO can be correctly predicted using regression models; prediction of PWT and LV diameters is not accurate.

Etiological profile of early neonatal bacterial sepsis by multiplex qPCR.

INTRODUCTION: Given the major impact in terms of morbidity and mortality that episodes of early neonatal sepsis (ENS) have on both newborns and health systems, this study aimed to identify the etiological profile of early neonatal bacterial sepsis by a multiplex quantitative real-time polymerase chain reaction (qPCR). METHODOLOGY: Blood samples from newborns diagnosed with clinical ENS and hospitalized in neonatal intensive care units (NICUs) were collected and analyzed using the multiplex qPCR method to detect Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter sp., Serratia sp., and Staphylococcus aureus. A universal primer was used in the analysis. RESULTS: A total of 150 neonates with clinical sepsis and 10 newborns as healthy controls were included in the study. The group with clinical sepsis was 100% positive for the presence of bacterial genomic DNA through the universal primer. The control group showed negativity by qPCR. The multiplex qPCR analysis showed that 76% of the samples were positive for Escherichia coli, 34% for Staphylococcus aureus, 13.3% for Streptococcus agalactiae, 7.3% for Pseudomonas aeruginosa, and 0.7% for Enterobacter sp. and Serratia sp. Multiplex qPCR of patients with clinical sepsis matched with 8.1% of the blood samples that tested positive by the microbiological method. CONCLUSIONS: Rapid and sensitive detection of the pathogens causing ENS by this new multi-target approach based on multiplex qPCR could potentially excel compared to microbiological methods, with the simple objective of facilitating the progression to a more rapid and specific antimicrobial therapy, avoiding the abuse of antibiotics in NICUs.

Effects of late exercise on cardiac remodeling and myocardial calcium handling proteins in rats with moderate and large size myocardial infarction.

BACKGROUND: Physical exercise attenuates myocardial infarction (MI)-induced cardiac remodeling. However, it is unsettled whether late exercise modulates post-infarction cardiac remodeling differentially according to infarct size. We investigated the effects of exercise started at late stage heart failure on cardiac remodeling in rats with moderate and large sized MI. METHODS: Three months after MI, rats were assigned into sedentary and exercise groups. Exercise rats underwent treadmill for three months. After assessing infarct size by histological analysis, rats were subdivided into four groups: moderate MI sedentary (Mod MI-Sed; n=7), Mod MI exercised (Mod MI-Ex; n=7), Large MI-Sed (n=11), and Large MI-Ex (n=10). RESULTS: Before exercise, MI-induced cardiac changes were demonstrated by comparing results to a Sham group; alterations were more intense in rats with large than moderate MI size. Systolic function, evaluated by echocardiogram using the variation in LV fractional area change between after and before exercise, was improved in exercise than sedentary groups. Calsequestrin expression increased in exercised compared to sedentary groups. L-type calcium channel was higher in Mod MI-Ex than Mod MI-Sed. SERCA2a, phospholamban, and Na(+)/Ca(2+) exchanger expression did not differ between groups. CONCLUSION: Late exercise improves systolic function and modulates intracellular calcium signaling proteins in rats with moderate and large MI.

AT1 receptor blockade attenuates insulin resistance and myocardial remodeling in rats with diet-induced obesity.

BACKGROUND: Although obesity has been associated with metabolic and cardiac disturbances, the carrier mechanisms for these responses are poorly understood. This study analyzed whether angiotensin II blockade attenuates metabolic and cardiovascular disorders in rats with diet-induced obesity. MATERIAL AND METHODS: Wistar-Kyoto (n = 40) rats were subjected to control (C; 3.2 kcal/g) and hypercaloric diets (OB; 4.6 kcal/g) for 30 weeks. Subsequently, rats were distributed to four groups: C, CL, OB, and OBL. L groups received Losartan (30 mg/kg/day) for five weeks. After this period we performed in vivo glucose tolerance and insulin tolerance tests, and measured triacylglycerol, insulin, angiotensin-converting enzyme activity (ACE), and leptin levels. Cardiovascular analyzes included systolic blood pressure (SBP), echocardiography, myocardial morphometric study, myosin heavy chain composition, and measurements of myocardial protein levels of angiotensin, extracellular signal-regulated (ERK1/2), c-Jun amino-terminal kinases (JNK), insulin receptor subunit ß (ßIR), and phosphatidylinositol 3-kinase (PI3K) by Western Blot. RESULTS: Glucose metabolism, insulin, lipid, and ACE activity disorders observed with obesity were minimized by Losartan. Moreover, obesity was associated with increased SBP, myocardial hypertrophy, interstitial fibrosis and improved systolic performance; these effects were also minimized with Losartan. On a molecular level, OB exhibited higher ERK, Tyr-phosphorylated ßIR, and PI3K expression, and reduced myocardial angiotensin and JNK expression. ERK and JNK expression were regulated in the presence of Losartan, while angiotensin, Tyr-ßRI, total and Tyr-phosphorylated PI3K expression were elevated in the OBL group. CONCLUSION: Angiotensin II blockade with Losartan attenuates obesity-induced metabolic and cardiovascular changes.

Extensive impact of saturated fatty acids on metabolic and cardiovascular profile in rats with diet-induced obesity: a canonical analysis.

BACKGROUND: Although hypercaloric interventions are associated with nutritional, endocrine, metabolic, and cardiovascular disorders in obesity experiments, a rational distinction between the effects of excess adiposity and the individual roles of dietary macronutrients in relation to these disturbances has not previously been studied. This investigation analyzed the correlation between ingested macronutrients (including sucrose and saturated and unsaturated fatty acids) plus body adiposity and metabolic, hormonal, and cardiovascular effects in rats with diet-induced obesity. METHODS: Normotensive Wistar-Kyoto rats were submitted to Control (CD; 3.2 Kcal/g) and Hypercaloric (HD; 4.6 Kcal/g) diets for 20 weeks followed by nutritional evaluation involving body weight and adiposity measurement. Metabolic and hormonal parameters included glycemia, insulin, insulin resistance, and leptin. Cardiovascular analysis included systolic blood pressure profile, echocardiography, morphometric study of myocardial morphology, and myosin heavy chain (MHC) protein expression. Canonical correlation analysis was used to evaluate the relationships between dietary macronutrients plus adiposity and metabolic, hormonal, and cardiovascular parameters. RESULTS: Although final group body weights did not differ, HD presented higher adiposity than CD. Diet induced hyperglycemia while insulin and leptin levels remained unchanged. In a cardiovascular context, systolic blood pressure increased with time only in HD. Additionally, in vivo echocardiography revealed cardiac hypertrophy and improved systolic performance in HD compared to CD; and while cardiomyocyte size was unchanged by diet, nuclear volume and collagen interstitial fraction both increased in HD. Also HD exhibited higher relative ß-MHC content and ß/α-MHC ratio than their Control counterparts. Importantly, body adiposity was weakly associated with cardiovascular effects, as saturated fatty acid intake was directly associated with most cardiac remodeling measurements while unsaturated lipid consumption was inversely correlated with these effects. CONCLUSION: Hypercaloric diet was associated with glycemic metabolism and systolic blood pressure disorders and cardiac remodeling. These effects directly and inversely correlated with saturated and unsaturated lipid consumption, respectively.

Disfunção miocárdica e alterações no trânsito de cálcio intracelular em ratos obesos / Myocardial dysfunction and abnormalities in intracellular calcium handling in obese rats

FUNDAMENTO: Vários mecanismos têm sido propostos contribuir para a disfunção cardíaca em modelos de obesidade, tais como alterações nas proteínas do trânsito de cálcio (Ca+2) e nos receptores beta-adrenérgicos. Todavia, o papel desses fatores no desenvolvimento da disfunção miocárdica induzida pela obesidade ainda não está claro. OBJETIVO: Este estudo pretende investigar se a obesidade induzida por um ciclo de dieta hipercalóricas resulta em disfunção cardíaca. Além disso, foi avaliado se essa alteração funcional em ratos obesos está relacionada com o prejuízo do trânsito de Ca+2 e do sistema beta-adrenérgico. MÉTODOS: Ratos Wistar machos, 30 dias de idade, foram alimentados com ração padrão (C) e um ciclo de cinco dietas hipercalóricas (Ob) por 15 semanas. A obesidade foi definida pelo aumento da porcentagem de gordura corporal dos ratos. A função cardíaca foi avaliada mediante análise isolada do músculo papilar do ventrículo esquerdo em condições basais e após manobras inotrópicas e lusitrópicas. RESULTADOS: Em comparação com o grupo controle, os ratos obesos apresentaram aumento da gordura corporal e intolerância a glicose. Os músculos dos ratos obesos desenvolveram valores basais semelhantes; entretanto, as respostas miocárdicas ao potencial pós-pausa e aumento de Ca+2 extracelular foram comprometidas. Não houve alterações na função cardíaca entre os grupos após a estimulação beta-adrenérgica. CONCLUSÃO: A obesidade promove disfunção cardíaca relacionada com alterações no trânsito de Ca+2 intracelular. Esse prejuízo funcional é provavelmente ocasionado pela redução da atividade da bomba de Ca+2 do retículo sarcoplasmático (SERCA2a) via Ca+2 calmodulina-quinase.

BACKGROUND: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca2+) handling proteins and β-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. OBJECTIVE: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca2+ handling and the β-adrenoceptor system. METHODS: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. RESULTS: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ were compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. CONCLUSION: Obesity promotes cardiac dysfunction related to changes in intracellular Ca2+ handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2) activation via Ca2+ calmodulin kinase.

Alterações vasculares em ratos obesos por dieta rica em gordura: papel da Via L-arginina/NO Endotelial / Vascular alterations in high-fat diet-obese rats: role of Endothelial L-arginine/NO Pathway / Alteraciones vasculares en ratones obesos por dieta rica en grasa: papel de la vía L-arginina/NO endotelial

FUNDAMENTO: Mecanismos subjacentes a anormalidades vasculares na obesidade ainda não estão completamente esclarecidos. OBJETIVO: Foi avaliada a via do óxido nítrico/L-arginina na resposta vascular de ratos obesos por dieta rica em gordura, enfocando as células endoteliais e do músculo liso. MÉTODOS: Ratos com 30 dias de vida foram divididos em 2 grupos: controle (C) e obeso (OB, ratos sob dieta rica em gordura por 30 semanas). Após 30 semanas, foram registrados o peso corporal, índice de adiposidade, pressão arterial e perfis metabólicos e endócrinos dos animais. Foram obtidas curvas para noradrelanina na ausência e presença de inibidor de óxido nítrico sintase (L-NAME, 3x10-4M) em aorta torácica intacta e com desnudamento em ratos C e OB. RESULTADOS: As medidas de peso corporal, índice de adiposidade, leptina e insulina aumentaram nos ratos OB, enquanto a pressão arterial permaneceu inalterada. A obesidade também produziu tolerância à glicose e resistência à insulina. A reatividade à noradrenalina da aorta intacta foi similar em ratos C e OB. A presença de L-NAME produziu um aumento similar nas respostas máximas, mas um desvio maior à esquerda das respostas nas aortas intactas dos ratos C em relação aos ratos OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presença de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs controle respectivo,†p < 0,05 vs controle mais L-NAME, n = 6-7]. Nenhum dos protocolos alterou a reatividade à noradrenalina de aortas com desnudamento. CONCLUSÃO: A obesidade induzida por dieta rica em gordura promove alterações metabólicas e vasculares. A alteração vascular envolveu uma melhora da via endotelial L-arginina/NO provavelmente relacionada à hiperinsulinemia e hiperleptinemia induzidas por dieta. A maior resistência aos efeitos do L-NAME na aorta de ratos obesos diz respeito a menor vulnerabilidade de indivíduos obesos na presença de patologias associadas que causam danos à atividade do sistema NO.

BACKGROUND: Mechanisms underlying vascular abnormalities in obesity remain to be completely clarified. OBJECTIVE: L-arginine/nitric oxide pathway was evaluated on vascular response of high-fat diet-obese rats, focusing on endothelial and smooth muscle cells. METHODS: 30-day-old rats were divided in two groups: control (C) and obese (OB, high-fat diet for 30 weeks). After 30 weeks, body weight, adiposity index, blood pressure, and metabolic and endocrine profiles of the animals were recorded. Curves to noradrenaline were obtained in absence and presence of nitric oxide synthase inhibitor (L-NAME, 3x10-4M) on intact and denuded thoracic aorta from C and OB rats. RESULTS: Body weight, adiposity index, leptin and insulin levels were increased in OB, while blood pressure was unchanged. Obesity also produced glucose tolerance and insulin resistance. Reactivity to noradrenaline of intact aorta was similar in C and OB rats. L-NAME presence produced a similar increase in maximal responses, but a higher leftward shift of noradrenaline responses in intact aorta from C than in OB rats [EC50 (x10-7M): C = 1.84 (0.83-4.07), O = 2.49 (1.41-4.38); L-NAME presence C = 0.02 (0.01-0.04)*, O = 0.21 (0.11-0.40)*†,*p < 0.05 vs respective control, †p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION: High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.

FUNDAMENTO: Los mecanismos subyacentes a las anormalidades vasculares en la obesidad todavía no están completamente aclarados. OBJETIVO: Se evaluó la vía del óxido nítrico/L-arginina en la respuesta vascular de ratones obesos por dieta rica en grasa, concentrándonos en las células endoteliales y en el músculo liso. MÉTODOS: Ratones con 30 días de vida que fueron divididos en 2 grupos: control (C) y obeso (OB, ratones bajo dieta rica en grasa durante 30 semanas). Después de 30 semanas, fueron registrados el peso corporal, el índice de adiposidad, la presión arterial y los perfiles metabólicos y endocrinos de los animales. Fueron obtenidas las curvas para noradrelanina en ausencia y en presencia del inhibidor de óxido nítrico sintasa (L-NAME, 3x10-4M), en la aorta torácica intacta y con denudación de los ratones C y OB. RESULTADOS: Las medidas de peso corporal, índice de adiposidad, leptina e insulina aumentaron en los ratones OB, mientras que la presión arterial permaneció inalterada. La obesidad también produjo una tolerancia a la glucosa y una resistencia a la insulina. La reactividad a la noradrenalina de la aorta intacta fue similar en los ratones C y OB. La presencia de L-NAME generó un aumento similar en las respuestas máximas, pero una desviación mayor a la izquierda de las respuestas en las aortas intactas de los ratones C con relación a los ratones OB [EC50 (x10-7M): C = 1,84 (0,83-4,07), O = 2,49 (1,41-4,38); presencia de L-NAME C = 0,02 (0,01-0,04)*, O = 0,21 (0,11-0,40)*†,*p < 0,05 vs control respectivo, †p < 0,05 vs control más L-NAME, n = 6-7]. Ninguno de los protocolos alteró la reactividad a la noradrenalina de las aortas con denudación. CONCLUSIÓN: La obesidad inducida por dieta rica en grasa genera alteraciones metabólicas y vasculares. La alteración vascular conllevó a una mejoría de la vía endotelial L-arginina/NO tal vez relacionada con la hiperinsulinemia e hiperleptinemia inducidas por dieta. La mayor resistencia a los efectos del L-NAME en la aorta de ratones obesos, se refiere a una menor vulnerabilidad de individuos obesos en presencia de patologías asociadas que causan daños a la actividad del sistema NO.

Myocardial dysfunction and abnormalities in intracellular calcium handling in obese rats.

BACKGROUND: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca²âº) handling proteins and ß-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. OBJECTIVE: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca²âº handling and the ß-adrenoceptor system. METHODS: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. RESULTS: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca²âº were compromised. There were no changes in cardiac function between groups after ß-adrenergic stimulation. CONCLUSION: Obesity promotes cardiac dysfunction related to changes in intracellular Ca²âº handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca²âº ATPase (SERCA2) activation via Ca²âº calmodulin kinase.