ANGIOTENSIN-(1-7) TREATMENT EARLY IN LIFE PREVENTS CARDIAC HYPERTROPHY IN ADULT HYPERTENSIVE RATS.

Angiotensin (Ang)-(1-7) is a cardioprotective peptide of the renin-angiotensin system. Pre-puberty has been considered as a later susceptible window of development and stressful factors in this life phase can induce chronic diseases in adulthood. We aimed to investigate whether the treatment with Ang-(1-7) during the pre-puberty could attenuate the development of hypertension and cardiac injury in adult spontaneously hypertensive rats (SHR). SHR were treated with Ang-(1-7) (24 µg/Kg/h) from 4 to 7 weeks of age. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography up to 17th of age. Thereafter, echocardiography was performed and the rats were euthanized for aorta reactivity assay and tissues and blood collections. Ang- (1-7) did not change the SBP and aortic reactivity but reduced the septal and posterior wall thickness, cardiomyocyte hypertrophy and fibrosis in SHR. Additionally, Ang-(1-7) reduced the gene expression of ANP and BNP, increased the metalloproteinase 9 expression, and reduced the ERK 1/2 phosphorylation. Ang-(1-7) also prevented the reduction of Mas receptor but did not change the protein expression of ACE2, ACE, AT1, and AT2. The treatment with Ang-(1-7) decreased the MDA levels and increased SOD-1 and catalase activity and protein expression of catalase. Our findings demonstrate that the treatment of SHR with Ang-(1-7) for three weeks early in life promotes beneficial effects in the heart later in life, even without altering blood pressure, through mechanisms involving the reduction of oxidative stress and ERK1/2 phosphorylation. Additionally, this study supports the pre-puberty as an important programming window.

Puberty as a DOHaD programming window: high-fat diet induces long-term hepatic dysfunction in male rats.

The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (-34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high ß-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

Combinatorial analysis of ACE and ACE2 polymorphisms reveals protection against COVID-19 worsening: A genetic association study in Brazilian patients.

Since angiotensin-converting enzyme 2, ACE2, was identified as the receptor for SARS-CoV-2 and considering the intense physiological interplay between the two angitensinases isoforms, ACE and ACE2, as counter-regulatory axis of the renin-angiotensin system, we proposed the evaluation of polymorphisms in these two key regulators in relation to COVID-19 severity. A genetic association study involving 621 COVID-19 hospitalized patients from Brazil was performed. All subjects had a confirmed diagnosis of COVID-19 via RT-PCR. Patients were categorized into two groups: the "mild" group (N = 296), composed of individuals hospitalized in ward beds who progressed to cure, and the "severe" group (N = 325), composed of individuals who required hospitalization in an intensive care unit (ICU), or who died. Blood samples were genotyped for ACE I/D polymorphism and ACE2 G8790A polymorphism by real-time PCR via TaqMan assay. The analysis of combined polymorphisms revealed a protective role for genotypic profile II/A_ (ORA = 0,26; p = 0,037) against the worsening of COVID-19 in women. The results indicate a protection profile to COVID-19 progression, in which the II/A_ carriers have almost four times less chance of a severe outcome. It is proposed that a decreased activity of ACE (deleterious effects) in conjunction with an increased ACE2 activity (protective effects), should be the underlying mechanism. The findings are unprecedented once other studies have not explored the genotypic combination analysis for ACE and ACE2 polymorphisms and bring perspectives and expectations for dealing with the COVID-19 pandemic based on definitions of genetically-based risk groups within the context of personalized medicine.

A comparative analysis of depressive-like behavior: Exploring sex-related differences and insights.

Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.

A peptide fraction from hardened common beans (Phaseolus vulgaris) induces endothelium-dependent antihypertensive and renal effects in rats.

Beans reached the research spotlight as a source of bioactive compounds capable of modulating different functions. Recently, we reported antioxidant and oxidonitrergic effect of a low molecular weight peptide fraction (<3 kDa) from hardened bean (Phaseolus vulgaris) in vitro and ex vivo, which necessitate further in vivo assessments. This work aimed to evaluate the hypotensive effect and the involved physiological mechanisms of the hardened common bean peptide (Phaseolus vulgaris) in normotensive (Wistar) and hypertensive (SHR) animals. Bean flour was combined with a solution containing acetonitrile, water and formic acid (25: 24: 1). Protein extract (PV3) was fractioned (3 kDa membrane). We assessed PV3 effects on renal function and hemodynamics of wistar (WT-normotensive) and spontaneously hypertensive rats (SHR) and measured systemic arterial pressure and flow in aortic and renal beds. The potential endothelial and oxidonitrergic involvements were tested in isolated renal artery rings. As results, we found that PV3: I) decreased food consumption in SHR, increased water intake and urinary volume in WT, increased glomerular filtration rate in WT and SHR, caused natriuresis in SHR; II) caused NO- and endothelium-dependent vasorelaxation in renal artery rings; III) reduced arterial pressure and resistance in aortic and renal vascular beds; IV) caused antihypertensive effects in a dose-dependent manner. Current findings support PV3 as a source of bioactive peptides and raise the potential of composing nutraceutical formulations to treat renal and cardiovascular diseases.

Angiotensin-(1-7) attenuates the negative inotropic response to acetylcholine in the heart.

Previous studies have suggested that the Angiotensin-(1-7) [(Ang-(1-7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1-7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1-7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1-7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dtmax, and dP/dtmin, but did not modify the hypotensive effect of ACh. Similarly, Ang-(1-7) attenuated the reduction of the LVESP, dP/dtmax, and dP/dtmin evoked by ACh in isolated hearts. These effects were blocked by the Mas receptor antagonist, A-779, but not by the adenylyl cyclase inhibitor MDL-12,330 A. Ang-(1-7) also attenuated the reduction in the maximum contraction and relaxation speeds and the shortening promoted by ACh in isolated cardiomyocytes. These data show that Ang-(1-7) acting through Mas receptor counter-regulates the myocardial contractile response to ACh in an arterial pressure and heart rate-independent manner.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19

Abstract Introduction The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Maternal postnatal early overfeeding induces sex-related cardiac dysfunction and alters sexually hormones levels in young offspring.

Postnatal early overfeeding (PO) is a risk factor for cardiometabolic disorders. However, remains unknown the cardiac effects in the second generation from postnatal overfed dams. Our aim was to investigate the effects of maternal PO on cardiac parameters in second generation (F2) offspring. For this, pregnant Wistar rats (F0) were divided into two groups: normal litter (NL, 9 pups) and small litter (SL, 3 pups). At P70, female offspring (F1) of both groups were mated with non-PO male rats. At P21 male and female F2 offspring (NLO and SLO) were weaned, and at P45 they were euthanized to evaluate the cardiac function and sample collection. Male and female SLO showed increased body weight, food intake and adiposity. Blood estradiol levels were increased in the male SLO and decreased in the female SLO. Blood testosterone levels increased in SLO females, but not change in SLO male rats. Although SLO offspring presented cardiac hypertrophy, only males had ex vivo functional impairments, such as reduction of the intraventricular systolic pressure and dP/dt. Male and female SLO had increased interstitial fibrosis; however, only the male SLO had increased perivascular fibrosis. In addition, only male rats from SLO group had decreased AKT and Type 2 Ang-2 receptor, increased catalase and type alpha estrogenic receptor protein levels. Maternal PO leads to obese phenotype and alters sex-steroid levels in both male and female offspring. Although both sexes showed cardiac hypertrophy, only male offspring showed cardiac dysfunction, which may be related with Ang2 and AKT signaling impairments.

Dysregulation in erythrocyte dynamics caused by SARS-CoV-2 infection: possible role in shuffling the homeostatic puzzle during COVID-19.

Introduction: The evolving COVID-19 pandemic became a hallmark in human history, not only by changing lifestyles, but also by enriching scientific knowledge on viral infection and its consequences. Objective: Although the management of cardiorespiratory changes is pivotal to a favorable prognosis during severe clinical findings, dysregulation of other systems caused by SARS-CoV-2 infection may imbalance erythrocyte dynamics, such as a bidirectional positive feedback loop pathophysiology. Method and Results: Recent evidence shows that SARS-CoV-2 is capable of affecting the genetics and dynamics of erythrocytes and this coexists with a non-homeostatic function of cardiovascular, respiratory and renal systems during COVID-19. In hypothesis, SARS-CoV-2-induced systematical alterations of erythrocytes dynamics would constitute a setpoint for COVID-19-related multiple organ failure syndrome and death. Conclusion: The present review covers the most frequent erythrocyte-related non-homeostatic findings during COVID-19 capable of providing mechanistic clues of SARS-CoV-2-induced infection and inspiring therapeutic-oriented scientific evidence.

Heterocyclic Compounds: Pharmacology of Pyrazole Analogs From Rational Structural Considerations.

Low quality of life and life-threatening conditions often demand pharmacological screening of lead compounds. A spectrum of pharmacological activities has been attributed to pyrazole analogs. The substitution, replacement, or removal of functional groups on a pyrazole ring appears consistent with diverse molecular interactions, efficacy, and potency of these analogs. This mini-review explores cytotoxic, cytoprotective, antinociceptive, anti-inflammatory, and antidepressant activities of some pyrazole analogs to advance structure-related pharmacological profiles and rational design of new analogs. Numerous interactions of these derivatives at their targets could impact future research considerations and prospects while offering opportunities for optimizing therapeutic activity with fewer adverse effects.

Medullary Noradrenergic Neurons Mediate Hemodynamic Responses to Osmotic and Volume Challenges.

Despite being involved in homeostatic control and hydro-electrolyte balance, the contribution of medullary (A1 and A2) noradrenergic neurons to the hypertonic saline infusion (HSI)-induced cardiovascular response after hypotensive hemorrhage (HH) remains to be clarified. Hence, the present study sought to determine the role of noradrenergic neurons in HSI-induced hemodynamic recovery in male Wistar rats (290-320 g) with HH. Medullary catecholaminergic neurons were lesioned by nanoinjection of antidopamine-ß-hydroxylase-saporin (0.105 ng·nl-1) into A1, A2, or both (LES A1; LES A2; or LES A1+A2, respectively). Sham rats received nanoinjections of free saporin in the same regions (SHAM A1; SHAM A2; or SHAM A1+A2, respectively). After 15 days, rats were anesthetized and instrumented for cardiovascular recordings. Following 10 min of stabilization, HH was performed by withdrawing arterial blood until mean arterial pressure (MAP) reaches 60 mmHg. Subsequently, HSI was performed (NaCl 3 M; 1.8 ml·kg-1, i.v.). The HH procedure caused hypotension and bradycardia and reduced renal, aortic, and hind limb blood flows (RBF, ABF, and HBF). The HSI restored MAP, heart rate (HR), and RBF to baseline values in the SHAM, LES A1, and LES A2 groups. However, concomitant A1 and A2 lesions impaired this recovery, as demonstrated by the abolishment of MAP, RBF, and ABF responses. Although lesioning of only a group of neurons (A1 or A2) was unable to prevent HSI-induced recovery of cardiovascular parameters after hemorrhage, lesions of both A1 and A2 made this response unfeasible. These findings show that together the A1 and A2 neurons are essential to HSI-induced cardiovascular recovery in hypovolemia. By implication, simultaneous A1 and A2 dysfunctions could impair the efficacy of HSI-induced recovery during hemorrhage.

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity.

Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT - normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control - CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air-jet (10 L/min - restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR; (ii) different stimuli evoked pressor and tachycardic responses; (iii) CL and RI reduced pressor response to sound; (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR; (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI; (vi) air-jet increased pressure and heart rate; (vii) CL or RI attenuated the pressor responses to air-jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air-jet-induced tachycardia.

Antiepileptic effects of long-term intracerebroventricular infusion of angiotensin-(1-7) in an animal model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE.

Brain and kidney GHS-R1a underexpression is associated with changes in renal function and hemodynamics during neurogenic hypertension.

Ghrelin is a peptide hormone whose effects are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), mainly expressed in the brain but also in kidneys. The hypothesis herein raised is that GHS-R1a would be player in the renal contribution to the neurogenic hypertension pathophysiology. To investigate GHS-R1a role on renal function and hemodynamics, we used Wistar (WT) and spontaneously hypertensive rats (SHR). First, we assessed the effect of systemically injected vehicle, ghrelin, GHS-R1a antagonist PF04628935, ghrelin plus PF04628935 or GHS-R1a synthetic agonist MK-677 in WT and SHR rats housed in metabolic cages (24 h). Blood and urine samples were also analyzed. Then, we assessed the GHS-R1a contribution to the control of renal vasomotion and hemodynamics in WT and SHR. Finally, we assessed the GHS-R1a levels in brain areas, aorta, renal artery, renal cortex and medulla of WT and SHR rats using western blot. We found that ghrelin and MK-677 changed osmolarity parameters of SHR, in a GHS-R1a-dependent manner. GHS-R1a antagonism reduced the urinary Na+ and K+ and creatinine clearance in WT but not in SHR. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a protein levels were decreased in the kidney and brain areas of SHR when compared to WT. Therefore, GHS-R1a role in the control of renal function and hemodynamics during neurogenic hypertension seem to be different, and this may be related to brain and kidney GHS-R1a downregulation.

Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats.

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.

Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice.

Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/kg, MLE (4, 20, or 100 mg/kg), fractions (F1 to F6), lupeol 10 mg/kg or diazepam (3 mg/kg). Methanolic leaf extract preserved neuron viability as well as the relative organ weight, and hematological and biochemical parameters. The behavioral endpoints, neuromuscular coordination, and sensory response parameters revealed a dose-dependent effect of methanolic leaf extract. This extract, active fractions, lupeol, and diazepam potentiated the hypno-sedative effect of the barbiturate and attenuated PTZ-induced acute seizure. This antiseizure effect was completely reversed by flumazenil 2 mg/kg (benzodiazepine site antagonist). Altogether, the benzodiazepine site-mediated anticonvulsant effects of methanolic leaf extract, active fractions, and lupeol corroborate traditional application of T. globiferus against epilepsy.

Long-term effects of early overfeeding and food restriction during puberty on cardiac remodeling in adult rats.

Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.

Exponential model for analysis of heart rate responses and autonomic cardiac modulation during different intensities of physical exercise.

The aim of this study was to compare the heart rate (HR) dynamics and variability before and after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) protocols with workloads based on treadmill workload at which maximal oxygen uptake was achieved ( WL V ˙ O 2 max ) . Ten participants performed cardiopulmonary exercise testing (CPET) to obtain oxygen uptake ( WL V ˙ O 2 max ) . All training protocols were performed on a treadmill, with 0% grade, and had similar total distance. The MICT was composed by 21 min at 70% of WL V ˙ O 2 max . The first HIIT protocol (HIIT-30 : 30) was composed by 29 repetitions of 30 s at 100% of s V ˙ O 2 max and the second HIIT protocol (HIIT-4 : 3) was composed by three repetitions of 4 min at 90% of WL V ˙ O 2 max . Before, during and after each training protocol, HR dynamics and variability (HRV) were analysed by standard kinetics and linear (time and frequency domains). The repeated measures analysis of variance indicated that the HR dynamics, which characterizes the speed of HR during the rest to exercise transition, was statistically (p < 0.05) slower during MICT in comparison to both HIIT protocols. The HRV analysis, which characterizes the cardiac autonomic modulation during the exercise recovery, was statistically higher in HIIT-4 : 3 in comparison to MICT and HIIT-30 : 30 protocols (p < 0.005 and p = 0.012, respectively), suggesting that the HIIT-4 : 3 induced higher sympathetic and lower parasympathetic modulation during exercise in comparison to the other training protocols. In conclusion, HIIT-4 : 3 demonstrated post-exercise sympathetic hyperactivity and a higher HRpeak, while the HIIT-30 : 30 and MICT resulted in better HRV and HR in the exercise-recovery transition. The cardiac autonomic balance increased in HIIT-30 : 30 while HIIT-4 : 3 induced sympathetic hyperactivity and cardiac overload.

Evaluation of the autonomic nervous system by analysis of heart rate variability in the preterm infants.

BACKGROUND: Premature infants may present with damage to the autonomic nervous system (ANS), which may be related to poorer neurological development. Among the techniques used to evaluate the ANS, heart rate variability (HRV) emerged as a simple, non-invasive, and easy to apply tool. The aim of the present study was to analyze and compare HRV in preterm infants at different times of hospitalization in order to verify the possible environmental relationships or clinical evolution with HRV. METHODS: A longitudinal, prospective, and descriptive study with non-probabilistic sampling composed of 25 collections of preterm infants of HRV at two moments: moment I (within 15 days of birth) and moment II (after 45 days post-birth). The Polar V800 heart rate monitor was used with the Polar H10 cardiac transducer to collect HRV, which was collected in the supine position for 15 min. The HRV data were analyzed by the linear method in frequency domain and time domain and by the nonlinear method using Kubios HRV analysis software, version 3.0.2. RESULTS: There was an increase in HRV values at moment II, these being statistically significant in the SD1, ApEn, and SampEn. Data related to increased sympathetic nervous system activity, parasympathetic nervous system activity, and increased index complexity. CONCLUSIONS: The data demonstrate an increase in HRV values in premature infants at moment II, demonstrating a possible development in the maturation of the ANS during hospitalization. TRIAL REGISTRATION: RBR-3x7gz8 retrospectively registered.

Forced internal desynchrony induces cardiometabolic alterations in adult rats.

Disruptions in circadian rhythms have been associated with several diseases, including cardiovascular and metabolic disorders. Forced internal desynchronization induced by a period of T-cycles of 22 h (T22 protocol) reaches the lower limit of entrainment and dissociates the circadian rhythmicity of the locomotor activity into two components, driven by different outputs from the suprachiasmatic nucleus (SCN). The main goal of this study was to evaluate the cardiovascular and metabolic response in rats submitted to internal desynchronization by T22 protocol. Male Wistar rats were assigned to either a control group subjected to a usual T-cycles of 24 h (12 h-12 h) or an experimental group subjected to the T22 protocol involving a 22-h symmetric light-dark cycle (11 h-11 h). After 8 weeks, rats subjected to the T22 exhibited desynchrony in their locomotor activity. Although plasma glucose and insulin levels were similar in both groups, desynchronized rats demonstrated dyslipidemia, significant hypertrophy of the fasciculate zone of the adrenal gland, low IRB, IRS2, PI3K, AKT, SOD and CAT protein expression and an increased expression of phosphoenolpyruvate carboxykinase in the liver. Furthermore, though they maintained normal baseline heart rates and mean arterial pressure levels, they also presented reduced baroreflex sensitivity. The findings indicate that circadian timing desynchrony following the T22 protocol can induce cardiometabolic disruptions. Early hepatic metabolism dysfunction can trigger other disorders, though additional studies are needed to clarify the causes.