Chronic pain recruits hypothalamic dynorphin/kappa opioid receptor signalling to promote wakefulness and vigilance.

Increased vigilance in settings of potential threats or in states of vulnerability related to pain is important for survival. Pain disrupts sleep and conversely, sleep disruption enhances pain, but the underlying mechanisms remain unknown. Chronic pain engages brain stress circuits and increases secretion of dynorphin, an endogenous ligand of the kappa opioid receptor (KOR). We therefore hypothesized that hypothalamic dynorphin/KOR signalling may be a previously unknown mechanism that is recruited in pathological conditions requiring increased vigilance. We investigated the role of KOR in wakefulness, non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in freely moving naïve mice and in mice with neuropathic pain induced by partial sciatic nerve ligation using EEG/EMG recordings. Systemic continuous administration of U69,593, a KOR agonist, over 5 days through an osmotic minipump decreased the amount of NREM and REM sleep and increased sleep fragmentation in naïve mice throughout the light-dark sleep cycle. We used KORcre mice to selectively express a Gi-coupled designer receptor activated by designer drugs (Gi-DREADD) in KORcre neurons of the hypothalamic paraventricular nucleus, a key node of the hypothalamic-pituitary-adrenal stress response. Sustained activation of Gi-DREADD with clozapine-N-oxide delivered in drinking water over 4 days, disrupted sleep in these mice in a similar way as systemic U69,593. Mice with chronic neuropathic pain also showed disrupted NREM and total sleep that was normalized by systemic administration of two structurally different KOR antagonists, norbinaltorphimine and NMRA-140, currently in phase II clinical development, or by CRISPR/Cas9 editing of paraventricular nucleus KOR, consistent with endogenous KOR activation disrupting sleep in chronic pain. Unexpectedly, REM sleep was diminished by either systemic KOR antagonist or by CRISPR/Cas9 editing of paraventricular nucleus KOR in sham-operated mice. Our findings reveal previously unknown physiological and pathophysiological roles of dynorphin/KOR in eliciting arousal. Physiologically, dynorphin/KOR signalling affects transitions between sleep stages that promote REM sleep. Furthermore, while KOR antagonists do not promote somnolence in the absence of pain, they normalized disrupted sleep in chronic pain, revealing a pathophysiological role of KOR signalling that is selectively recruited to promote vigilance, increasing chances of survival. Notably, while this mechanism is likely beneficial in the short-term, disruption of the homeostatic need for sleep over longer periods may become maladaptive resulting in sustained pain chronicity. A novel approach for treatment of chronic pain may thus result from normalization of chronic pain-related sleep disruption by KOR antagonism.

Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Assessment of patients' knowledge and preferences for the use of orthodontic aligners.

OBJECTIVE: To evaluate the knowledge and preference of patients treated at a Dental School in Jaraguá do Sul, Brazil, about using aligners and the reasons for choosing this device as a treatment option. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 82 participants aged 18-45 years recruited at a screening clinic. METHODS: A questionnaire was completed in person using a tablet with digital forms. RESULTS: Almost half of the participants (49%) knew about aligners; 40% were aged 18-24 years, and 77% were female. When observing the images of the types of orthodontic appliances, the aligners had an acceptance rate of 80%. Among the reasons that led to the preference for choosing aligners, 68% cited aesthetics and 42% comfort. CONCLUSION: Recently, clear aligners have become a popular choice for orthodontic treatment, particularly among adults. Despite their popularity and effectiveness, many patients still need more information about aligner treatment. Over half of the respondents did not know what orthodontic aligners were. Younger participants had more knowledge about aligners than older participants. Patients still need more knowledge about the types of appliances available for orthodontic treatment. When presented with images of the kinds of devices available, almost 80% of participants showed greater satisfaction with aligners.

Tracheal regeneration with acellular human amniotic membrane and 15-deoxy-∆12,14prostaglandinj2 nanoparticles in a rabbit model.

The treatment of tracheal pathologies remains challenging.Nanotechnology allows adding substances to decellularized human amniotic membrane (DHAM), such as 15-Deoxy-∆12,14ProstaglandinJ2 nanoparticles (15D-PGJ2-NC).This study performed a tracheotomy in rabbits randomized into three groups.The tissue repair process was evaluated when treated with DHAM associated or not with 15D-PGJ2-NC.The average of the area in the control group was 54.76% smaller than DHAM group and 41.98% smaller than DHAM + 15D-PGJ2-NC group (p=0.004 for both).The DHAM + 15D-PGJ2-NC group had significantly more immature cartilage (p=0.015).DHAM impregnated with 15D-PGJ2-NC could provide support for the healing of the tracheal defect and may prevent reduction of its lumen.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Animal rights, environment, or health? Effects of argument type and dissonance on the attitudes toward the consumption of animals.

The scientific literature and advocacy organisations highlight three harm-related arguments as paramount reasons for the reduction and cessation of the consumption of animal-derived products (ADP) - violence toward animals, damage to the environment, and human health. However, research on their comparative effects is scarce and there is no clear definition of which type of argument is the most effective in restricting ADP consumption. Based on cognitive dissonance theory, this study aimed to investigate the effects of these types of arguments on meat-eaters' attitudes and beliefs toward the propositions of reducing and ceasing ADP consumption. The study sample comprised 545 Brazilian adults. We adopted an experimental between-subjects design based on the presentation of vignettes. Each participant responded to one of the vignettes (animal rights, environmental, or health arguments) or a control condition. Results showed that greater levels of ADP-related dissonance provoked greater positive attitudes toward the reduction and cessation of ADP consumption. Compared to baseline, the animal rights and environmental messages significantly increased dissonance and positive attitudes toward ADP restriction, but not the health argument. Participants most frequently adopted the dissonance-management strategies of denial of responsibility, denial of harm, and the articulation of beliefs favourable to change. The discussion highlights that the different effects of social influence contexts and argument types depend on their capacity to reveal ADP consumption as morally problematic behaviour. To our knowledge, this is the first study to experimentally compare the effects of animal rights, environmental and health-related arguments in generating ADP-related dissonance and attitude change.

Exploring the neurobiology of the premonitory phase of migraine preclinically - a role for hypothalamic kappa opioid receptors?

BACKGROUND: The migraine premonitory phase is characterized in part by increased thirst, urination and yawning. Imaging studies show that the hypothalamus is activated in the premonitory phase. Stress is a well know migraine initiation factor which was demonstrated to engage dynorphin/kappa opioid receptors (KOR) signaling in several brain regions, including the hypothalamus. This study proposes the exploration of the possible link between hypothalamic KOR and migraine premonitory symptoms in rodent models. METHODS: Rats were treated systemically with the KOR agonist U-69,593 followed by yawning and urination monitoring. Apomorphine, a dopamine D1/2 agonist, was used as a positive control for yawning behaviors. Urination and water consumption following systemic administration of U-69,593 was also assessed. To examine if KOR activation specifically in the hypothalamus can promote premonitory symptoms, AAV8-hSyn-DIO-hM4Di (Gi-DREADD)-mCherry viral vector was microinjected into the right arcuate nucleus (ARC) of female and male KORCRE or KORWT mice. Four weeks after the injection, clozapine N-oxide (CNO) was administered systemically followed by the assessment of urination, water consumption and tactile sensory response. RESULTS: Systemic administration of U-69,593 increased urination but did not produce yawning in rats. Systemic KOR agonist also increased urination in mice as well as water consumption. Cell specific Gi-DREADD activation (i.e., inhibition through Gi-coupled signaling) of KORCRE neurons in the ARC also increased water consumption and the total volume of urine in mice but did not affect tactile sensory responses. CONCLUSION: Our studies in rodents identified the KOR in a hypothalamic region as a mechanism that promotes behaviors consistent with clinically-observed premonitory symptoms of migraine, including increased thirst and urination but not yawning. Importantly, these behaviors occurred in the absence of pain responses, consistent with the emergence of the premonitory phase before the headache phase. Early intervention for preventive treatment even before the headache phase may be achievable by targeting the hypothalamic KOR.

Germination and Post-Seminal Development of Mimosa L. (Fabaceae) in Diesel Oil-Contaminated Soil.

Germination and post-seminal development are important stages for the establishment of plants and for determining their tolerance to diesel oil. Diesel-tolerant species can contribute to the recovery of contaminated areas, and leguminous plants are promising in the treatment of contaminated soil through nitrogen fixation. This study identified the effects of diesel oil-contaminated soil on the germination and seedlings of the leguminous species Mimosa bimucronata, M. flocculosa, and M. scabrella var. aspericarpa. The experiment comprised two treatments contaminated (4% concentration) and uncontaminated soil and was performed in a greenhouse for 90 days, with evaluations 30, 60, and 90 days after sowing. Germination was not affected, but most root and aerial system parameters were statistically lower in contaminated soil, indicating low initial development potential in soil contaminated with diesel oil. Moreover, the negative effects increased with higher exposure time to the contaminant.

Vatairea guianensis lectin stimulates changes in gene expression and release of TNF-α from rat peritoneal macrophages via glycoconjugate binding.

Using a rat model of peritonitis, we herein report the inflammatory effect induced by the lectin isolated from Vatairea guianensis (VGL) seeds in the context of interactions between VGL and both toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1). Peritoneal macrophages were stimulated with VGL for dose-dependent gene expression and release of TNF-α. In vivo results showed that VGL (1 mg/kg; intraperitoneal) induced peritonitis in female Wistar rats. Leukocyte migration, macrophage activation, and protein leakage were measured 3 and 6 hours after induction. In vitro, peritoneal macrophages were stimulated with VGL for gene expression and TNF-α dosage (mean ± SEM (n = 6), analysis of variance, and Bonferroni's test (P < .05)). In silico, VGL structure was applied in molecular docking with representative glycans. It was found that (a) VGL increases vascular permeability and stimulates leukocyte migration, both rolling and adhesion; (b) lectin-induced neutrophil migration occurs via macrophage stimulation, both in vitro and in vivo; (c) lectin interacts with TLR4 and TNFR1; and (d) stimulates TNF-α gene expression (RT-PCR) and release from peritoneal macrophages. Thus, upon lectin-glycan binding on the cell surface, our results suggest that VGL induces an acute inflammatory response, in turn activating the release of peritoneal macrophages via TNF-α and TLR and/or TNFR receptor pathways.

Synthesis of chalcones derived from 1-naphthylacetophenone and evaluation of their cytotoxic and apoptotic effects in acute leukemia cell lines.

Chalcones and their derivatives have been described as promising compounds with antiproliferative activity against leukemic cells. This study aimed to investigate the cytotoxic effect of three synthetic chalcones derived from 1-naphthylacetophenone (F07, F09, and F10) in acute leukemia cell lines (K562 and Jurkat) and examine the mechanisms of cell death induced by these compounds. The three compounds were cytotoxic to K562 and Jurkat cells, with IC50 values ranging from 1.03 to 31.66 µM. Chalcones induced intrinsic and extrinsic apoptosis, resulting in activation of caspase-3 and DNA fragmentation. F07, F09, and F10 were not cytotoxic to human peripheral blood mononuclear cells, did not produce any significant hemolytic activity, and did not affect platelet aggregation after ADP stimulation. These results, combined with calculations of molecular properties, suggest that chalcones F07, F09, and F10 are promising molecules for the development of novel antileukemic drugs.

Cell Cycle Arrest and Apoptosis Induction by a New 2,4-Dinitrobenzenesulfonamide Derivative In Acute Leukemia Cells.

BACKGROUND: Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat. METHODS: The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy. RESULTS: Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin.  Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells. CONCLUSION: Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs.

Fructose Intake Impairs Cortical Antioxidant Defenses Allied to Hyperlocomotion in Middle-Aged C57BL/6 Female Mice.

Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 12 weeks. After that, metabolic, and neurochemical alterations were evaluated, focusing on neurotransmitters, and antioxidant defenses. Behavioral parameters related to motor activity, memory, anxiety, and depression were also evaluated. Mice consuming FRU diet displayed increased water, and caloric intake, resulting in weight gain, which was partially compensated due to decreased food pellet intake. FRU fed animals displayed increased plasma glucose, and cholesterol levels, which was not observed in overnight-fasted animals. Superoxide dismutase (SOD), and catalase (CAT) activities were markedly decreased in the prefrontal cortex of animals receiving FRU diet, while glutathione peroxidase (GPx) slightly increased. Liver (lower GPx), striatum (higher SOD and lower CAT), and hippocampus (no changes) were less impacted. No changes were observed in glutathione reductase, and thioredoxin reductase activities, two ancillary enzymes for peroxide detoxification. FRU intake did not alter serotonin, dopamine, and norepinephrine levels in the hippocampus, prefrontal cortex, and striatum. No significant alterations were observed in working, and short-term spatial memory; and in anxiety- and depressive-like behaviors in animals treated with FRU. Increased locomotor activity was observed in FRU-fed middle-aged mice, as evaluated in the open field, elevated plus-maze, Y maze, and object location tasks. Overall, these results demonstrate that high FRU consumption can disturb antioxidant defenses, and increase locomotor activity in middle-aged mice, open the opportunity for further studies to address the underlying mechanisms related to these findings.

A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia.

Identification of allosteric inhibitors of PTPs has attracted great interest as a new strategy to overcome the challenge of discover potent and selective molecules for therapeutic intervention. YopH is a virulence factor of the genus Yersinia, validated as an antimicrobial target. The finding of a second substrate binding site in YopH has revealed a putative allosteric site that could be further exploited. Novel chalcone compounds that inhibit PTPs activity were designed and synthesized. Compound 3j was the most potent inhibitor, interestingly, with different mechanisms of inhibition for the panel of enzymes evaluated. Further, our results showed that compound 3j is an irreversible non-competitive inhibitor of YopH that binds to a site different than the catalytic site, but close to the well-known second binding site of YopH.

Activated carbon obtained from amazonian biomass tailings (acai seed): Modification, characterization, and use for removal of metal ions from water.

Acai seed was used herein as an Amazon biomass waste for the synthesis of activated and modified carbon in order to find a possible use for the large volume of residues generated during the processing of this fruit and to add value to this residue. Activated carbon materials were used to remove Pb2+, Fe2+, and Mg2+ metal ions from water. The efficiency of removal of these ions by the acai seed activated carbon was compared with that by commercial activated carbon. Activated carbon materials were prepared by carbonization and chemical activation using two KOH impregnation ratios, namely 1:1 (ACK1) and 5:1 (ACK5), by mass. These samples were modified by treatment with nitric acid under microwave heating (ACK1-M) and (ACK5-M), respectively. The result of the elemental analysis indicated that this biomass has carbon and sulfur contents of 43.29% and 0.10% wt, respectively. The textural parameters showed that the obtained activated carbon samples presented high surface areas between 1462 and 2774 m2 g-1. Raman analysis revealed the different degrees of graphitization of the activated carbon materials. Boehm titration identified the presence of phenolic, carboxylic, and lactonic groups in samples that were confirmed by Fourier transform infrared spectroscopy. In the metal adsorption tests, ACK5-M showed better removal efficiency, reaching 86% removal for Pb2+, 69% for Fe2+, and 8% for Mg2+in 1 h of contact time; these results were superior to those obtained for commercial carbon. The results indicated that acai seed can be used for the production of activated carbon and can also be used for metal removal.

Heterochromatin and numeric chromosome evolution in Bignoniaceae, with emphasis on the Neotropical clade Tabebuia alliance.

Bignoniaceae is a diverse family composed of 840 species with Pantropical distribution. The chromosome number 2n = 40 is predominant in most species of the family, with n = 20 formerly being considered the haploid base number. We discuss here the haploid base number of Bignoniaceae and examine heterochromatin distributions revealed by CMA/DAPI fluorochromes in the Tabebuia alliance, as well as in some species of the Bignonieae, Tecomeae, and Jacarandeae tribes. When comparing the chromosome records and the phylogenies of Bignoniaceae it can be deduced that the base number of Bignoniaceae is probably n = 18, followed by an ascendant dysploidy (n = 18 → n = 20) in the most derived and diverse clades. The predominant heterochromatin banding patterns in the Tabebuia alliance were found to be two terminal CMA+ bands or two terminal and two proximal CMA+ bands. The banding pattern in the Tabebuia alliance clade was more variable than seen in Jacarandeae, but less variable than Bignonieae. Despite the intermediate level of variation observed, heterochromatin banding patterns offer a promising tool for distinguishing species, especially in the morphologically complex genus Handroanthus.

Composting as a strategy to recycle aquatic animal waste: Case study of a research centre in São Paulo State, Brazil.

Aquaculture is a fast-growing activity in Brazil and around the world, which generates large amounts of waste from fingerling production to the final consumer. Among several possibilities for the management of these wastes, windrow composting stands out as a simple and low-cost method. In this study, 16 composting piles were assembled with wood shavings and peanut shells and managed according to two methods; one with carcasses recharges and another without. A description of the daily occurrences and management details were made. Temperature and moisture content were monitored and at the end of the decomposition process, and after 60 and 100 days of curing, physic-chemical analysis was performed to assess composts quality. A germination index test was performed to assess composts phytotoxicity. All piles exceeded 55 °C for more than 15 days (with the aid of turnings) and germination indices were above 50% for both lettuce and cress seeds. Total nitrogen concentration among composts varied from 22.1 to 33.2 g kg-1 and carbon:nitrogen ratios were below 20, while pH values were above 6.0 in all composts. Curing composts for 60 and 100 days did not influence any of the physic-chemical characteristics of all composts, so this practice can be dodged, thus avoiding unnecessary land use and increasing production costs. The type of management adopted for carcasses of aquatic animals influenced total and inorganic nitrogen, C/N ratio, organic matter and pH values of the composts, being recommended the recharge of carcasses to improve composts stability and quality.

Proteomic identification and purification of seed proteins from native Amazonian species displaying antifungal activity.

MAIN CONCLUSION: Seeds of native species from the rain forest (Amazon) are source of chitinases and their protein extracts exhibited strong and broad antifungal activity. Numerous plant species native to the Amazon have not yet been chemically studied. Studies of seeds are scarcer, since adversities in accessing study areas and seasonality pose constant hurdles to systematic research. In this study, proteins were extracted from seeds belonging to endemic Amazon species and were investigated for the first time. Proteolytic activity, peptidase inhibitors, and chitinases were identified, but chitinolytic activity predominated. Four proteins were purified through chromatography and identified as lectin and chitinases by MS/MS analyses. The proteins were examined for inhibition of a phytopathogen (Fusarium oxysporum). Analyses by fluorescence microscopy suggested binding of propidium iodide to DNA of fungal spores, revealing that spore integrity was lost when accessed by the proteins. Further structural and functional analyses of defensive proteins belonging to species facing highly complex ecosystems such as Amazonia should be conducted, since these could provide new insights into specificity and synergism involving defense proteins of plants submitted to a very complex ecosystem.

Acute Hypotension After Moderate-Intensity Handgrip Exercise in Hypertensive Elderly People.

Souza, LR, Vicente, JB, Melo, GR, Moraes, VC, Olher, RR, Sousa, IC, Peruchi, LH, Neves, RV, Rosa, TS, Ferreira, AP, and Moraes, MR. Acute hypotension after moderate-intensity handgrip exercise in hypertensive elderly people. J Strength Cond Res 32(10): 2971-2977, 2018-Isometric handgrip (IHG) training is effective in reducing blood pressure (BP), but little is known about the occurrence of acute hypotension by postisometric exercise hypotension (PIEH) and the underlying mechanisms. Ten sedentary hypertensive elderly people (7 women and 3 men) individuals, with a mean age of 73.2 ± 2.2 years and systolic BP (SBP) of 135.1 ± 6.5, were included; they were hypertensive for 13.2 ± 3.1 years and were receiving medications. These patients underwent 2 experimental sessions of isometric exercise using a portable hydraulic handgrip dynamometer: (a) sham session with 3% of maximal voluntary isometric contraction (MVIC) and (b) experimental isometric session with 30% MVIC, completing a total of 8 sets of 1-minute contraction and 1-minute rest-pause (overload of work = 51.7 kgf·min). Blood pressure and heart rate were evaluated at rest and 1, 5, 10, 15, 30, 45, and 60 minutes postexercise. Blood lactate (Lac) and salivary nitric oxide (NO) were collected at rest, 0, 30, and 60 minutes postexercise. The SBP presented a reduction as of the tenth minute postexercise to session 30% MVIC (Δ = -14.4 at -18.7 mm Hg, p < 0.05). At 60-minute postexercise, the SBP was 30% lower vs. 3% MVIC (-20.2 mm Hg, p = 0.006). There were no differences for the other cardiovascular parameters and vasoactive substances for both sessions (p > 0.05). These results demonstrated that the IHG exercise with a higher overload of work induced PIEH in hypertensive elderly people, but there was no association with Lac and NO. Therefore, this IHG model with easy execution, quick adherence, short duration, and a portable equipment can be an excellent adjuvant strategy for the control and prevention of hypertension.