José Eduardo da Silva Santos (original) (raw)

Papers by José Eduardo da Silva Santos

American Journal of Hypertension

The FASEB Journal, 2014

Hyporesponsiveness to vasoconstrictors is a well-known characteristic of septic shock. We hypothe... more Hyporesponsiveness to vasoconstrictors is a well-known characteristic of septic shock. We hypothesized that the degree of vascular hyporesponsiveness may vary among different vascular systems. Both aortic rings and perfused kidneys obtained from male Wistar rats treated with lipopolysaccharide (LPS; 10 mg/kg, i.p.) were evaluated for their reactivity to vasopressin (AVP), 6 and 24 h after LPS injection (LPS 6 and LPS 24 h groups, respectively). AVP-induced contraction was reduced by 30-80% in aortic rings from LPS 6 and 24 h groups, while perfused kidneys showed enhanced responses to AVP. For instance, AVP (10 pmol) increased the renal perfusion pressure by 27.5 ± 4.7, 95 ± 12.8, and 150.6 ± 11.4 mm Hg in control, LPS 6 and LPS 24 h groups, respectively. Western blotting analysis revealed increased levels of phosphorylated MYPT1 in kidneys, but not in aortas from LPS 6 and 24 h rats. Our results demonstrate that vascular systems may present different profiles of responses to vasoconstrictors during endoto...

International Dairy Journal, 2019

Abstract A vasorelaxant whey hydrolysate at semi-pilot scale was generated, assessing the influen... more Abstract A vasorelaxant whey hydrolysate at semi-pilot scale was generated, assessing the influence between two different enzyme inactivation conditions (pH and temperature) and drying technologies (freeze- and spray-drying). Hydrolysis was performed with 1.25% (w/v) whey protein concentrate solution and 1.91% (w/w) pepsin (pH 2, 3 h, 37 °C). Reactions were stopped either by increasing the pH to 7 (5 m NaOH) or by heating the solution at 80 °C for 5 min. Thermally inactivated samples induced a vascular relaxation ex vivo above 70%, while the chemically inactivated ones reached only 20%. Both drying technologies were effective in maintaining the bioactivity of the hydrolysate. These results brought the possibility of developing a whey-based product with high vasorelaxant potential in semi-pilot scale; thermal treatment followed by spray drying seemed to be the more affordable alternative for food and nutraceutical industries to generate this bioactive product.

Intensive care medicine experimental, 2017

Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasi... more Extracellular superoxide dismutase (ECSOD) protects nitric oxide (NO) bioavailability by decreasing superoxide levels and preventing peroxynitrite generation, which is important in maintaining renal blood flow and in preventing acute kidney injury. However, the profile of ECSOD expression after sepsis is not fully understood. Therefore, we intended to evaluate the content and gene expression of superoxide dismutase (SOD) isoforms in the renal artery and their relation to renal blood flow. Sepsis was induced in Wistar rats by caecal ligation and perforation. Several times after sepsis induction, renal blood flow (12, 24 and 48 h); the renal arterial content of SOD isoforms, nitrotyrosine, endothelial and inducible nitric oxide synthase (e-NOS and i-NOS), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP); and SOD activity (3, 6 and 12 h) were measured. The influence of a SOD inhibitor was also evaluated. An increase in ECSOD content was associated with decreased 3-nitro...

Canadian journal of physiology and pharmacology, 2014

Smoothelin-B (SMTL-B) and calponin-1 are important regulators of vascular contraction. SMTL-B con... more Smoothelin-B (SMTL-B) and calponin-1 are important regulators of vascular contraction. SMTL-B contains a calponin-homology domain and is structurally similar to cardiac troponin T. As calponin-1 and troponin T are proteolyzed by intracellular matrix metalloproteinase (MMP)-2 in oxidative stress injury, we hypothesized that SMTL-B is also cleaved by MMP-2 and contributes to lipopolysaccharide (LPS)-induced vascular hypocontractility. Rats received ONO-4817 (an MMP inhibitor) or its vehicle, 2 h prior to being administered lipopolysaccharide (LPS). LPS-induced aorta hypocontractility to potassium chloride or phenylephrine, and reduction of calponin-1 levels, were abolished by ONO-4817 at 6 but not 3 h after LPS. However, the level of SMTL-B was unaltered in LPS aortas and further unaffected by ONO-4817. Despite the importance of SMTL-B in vascular tone, it is not a target of MMP-2 in LPS-induced hypocontractility.

Shock, 2002

This study evaluated the involvement of nitric oxide (NO), guanylate cyclase, and potassium chann... more This study evaluated the involvement of nitric oxide (NO), guanylate cyclase, and potassium channels in the long-lasting vascular hyporesponsiveness to phenylephrine induced by Escherichia coli lipopolysaccharide (LPS) in vitro and in vivo. Experiments in rat aorta rings with endothelium incubated with LPS (10 µg/mL) for 12 h showed that the hyporesponsiveness depends on guanylate cyclase activity and tetraethylammonium-sensitive, but not voltage-or ATPdependent, potassium channels. Pressor responses to phenylephrine were reduced by 50% in rats injected 8 and 24 h before with LPS (10 mg/kg, intraperitoneally). Pretreatment with NO synthase inhibitors (iNOS; N-nitro-L-arginine methyl ester [L-NAME], 55 µmol/kg or aminoguanidine, 244 µmol/kg, intraperitoneally) fully prevented LPS-induced hyporesponsiveness. When administered just before phenylephrine, L-NAME (11 µmol/kg, intravenously) reversed the hyporesponsiveness in rats injected 8 h, but not in those injected 24 h before with LPS, whereas 1H-[1,2,4]-oxadiazolo-[4,3-a]quinoxalin-1 (ODQ, 11 µmol/kg, intravenously) reversed the hyporesponsiveness in animals injected 24 h, but not in those injected 8 h before with LPS. Tetraethylammonium (360 µmol/kg, intravenously) reestablished normal responses to phenylephrine in rats injected 8 and 24 h before with LPS. Again, neither voltage-nor ATP-dependent potassium channels appears to be involved. Western blot showed that iNOS expression peaked at 8 h, decreasing to low levels 24 h after LPS injection. Therefore, NO is important in initiating LPS-induced hyporesponsiveness to vasoconstrictors, but not in maintaining it for long periods. Once NO has exerted its effects and even when iNOS expression is minimal, the long-lasting hyporesponsiveness appears to depend on a complex interplay between guanylate cyclase and potassium channel activation.

Journal of Pharmacology and Experimental Therapeutics, 2002

Neutrophil activation and migration during an inflammatory response is preceded or accompanied by... more Neutrophil activation and migration during an inflammatory response is preceded or accompanied by plasma membrane electrical changes. Besides changes in calcium currents, neutrophils have a high permeability to potassium, mainly through potassium channels. However, the significance of potassium channels in neutrophil physiology is still unclear. Here, we show that the treatment of rats with the ATP-sensitive potassium channel blocker glibenclamide (4, 20, or 40 mol/kg) dose dependently decreased carrageenan-, N-formyl-methionylleucyl-phenylalanine (fMLP)-, and lipopolysaccharide-induced neutrophil influx and fluid leakage into the interpleural space.

$Research paper thumbnail of Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek (Celastraceae) leaves$

Journal of Ethnopharmacology, 2006

This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution pre... more This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution prepared from residues of methanolic extracts of ground leaves of Maytenus ilicifolia is able to cause a concentration-and endothelium-dependent relaxation in pre-contract rat aorta rings, with EC 50 of 199.7 (190-210) g/ml. The non-selective nitric oxide synthase inhibitors l-NAME and l-NMMA abolished this effect, while superoxide dismutase and MnTBAP (a non-enzymatic superoxide dismutase mimetic) enhanced it. Further, relaxation induced by this ethanolic supernatant have been strongly inhibited by the guanylate cyclase inhibitors methylene blue and ODQ, as well as by the potassium channel blockers 4aminopyridine and tetraethylammonium, but was unchanged by the cyclooxigenase inhibitor indomethacin and the membrane receptor antagonists atropine, HOE-140 and pirilamine. Partition of the ethanolic supernatant between H 2 O and EtOAc generated a fraction several times more potent, able to fully relax endothelium-intact aorta rings with an EC 50 of 4.3 (3.9-4.8) g/ml. 13 C NMR spectrum of this fraction showed signals typical of catechin. This study reveals that the leaves of M. ilicifolia possess one or more potent substances able to relax endothelium-intact rat aorta rings, an event that appears to involve nitric oxide production, guanylate cyclase activation and potassium channel opening.

Critical Care, 2013

Background: We hypothesized that one single episode of acute kidney injury (AKI) reduces long-ter... more Background: We hypothesized that one single episode of acute kidney injury (AKI) reduces long-term survival compared with no acute kidney injury (No AKI) following recovery from critical illness. Materials and methods: A prospective cohort of 2,010 patients admitted to the ICU between 2000 and 2009 at a provincial referral hospital was followed to determine whether AKI influences long-term survival. Results: Of the 1,844 eligible patients, 18.4% had AKI stage 1, 12.1% had stage 2, 26.5% had stage 3, and 43.0% had No AKI, using the KDIGO classification. The mean and median follow-up time was 8.1 and 8.7 years. The 28-day, 1-year, 5-year and 10-year survival rates were 59.6%, 44.9%, 37.4%, and 33.4%, in patients with any AKI (stage 1, stage 2, stage 3), which was significantly worse compared with the critically ill patients with no AKI at any time (P < 0.01). The adjusted 10-year mortality risk associated with AKI was 1.44 (95% CI = 1.2 to 1.7) among 28-day survivors. Patients who had mild AKI (stage 1) had significantly worse survival at 28 days, 1 year, 3 years, 5 years and 10 years compared with No AKI (P < 0.01) (Figure 1A). Patients with sepsis and AKI who survived 28 days had significantly poorer 5-year and 10-year survival compared with nonseptic AKI (P < 0.01) (Figure 1B). Conclusions: Patients with one episode of mild (stage 1) AKI have significantly lower survival rates over 10 years than critically ill patients without AKI. The causes and mechanisms of this association warrant further careful study. Close medical follow-up of these patients may be warranted and mechanistic research required understanding how AKI influences distant events.

The American Journal of Sports Medicine, 2007

Background An increase in matrix metalloproteinases (MMPs) and the resulting degradation of the e... more Background An increase in matrix metalloproteinases (MMPs) and the resulting degradation of the extracellular matrix have been implicated in the pathogenesis of tendinopathy. Studies have documented the beneficial effects of MMP inhibitors used to treat pathologic conditions in which MMP activity has had a negative effect on connective tissues. Hypothesis Matrix metalloproteinase inhibitors will prevent the decrease in material properties associated with tendon stress deprivation by inhibiting MMP activity. Study Design Controlled laboratory study. Methods Rat tail tendons were subjected to 7 days of in vitro stress deprivation with and without the addition of 1 of 2 broad-spectrum MMP inhibitors (doxycycline and ilomastat). The material properties (ultimate tensile stress, strain, and tensile modulus) of the tendons were compared with each other and with fresh control tendons. In addition, tendons from each group were evaluated for MMP-13 messenger RNA expression, MMP-13 protein sy...

Life Sciences, 2021

AIMS Post-occlusive reactive hyperemia (PORH) remains poorly understood in the skeletal muscle sy... more AIMS Post-occlusive reactive hyperemia (PORH) remains poorly understood in the skeletal muscle system. This study was designed to validate an alternative strategy of PORH detection in rodents. Additionally, we explored the hypothesis that PORH is influenced by experimental models associated with impaired function of the skeletal muscle. MATERIALS AND METHODS Wistar rats were anesthetized, and blood flow was assessed by laser Doppler in the anterior tibialis muscle, before and immediately after 5 s, 30 s, 3 min, or 5 min of flow occlusion, obtained through a cuff inflated to 300 mmHg around the thigh of the animals. KEY FINDINGS In healthy animals, deflating the cuff resulted in a fast increment of local blood flow, characterizing the PORH after 5 s to 5 min of cuff occlusion and its dependence on flow occlusion duration. Importantly, we found different profiles of PORH in animals pretreated with reserpine (accelerated peak and reduced half recovery time), streptozotocin (increased peak), or subjected to muscle contraction in stretching (delayed peak), approaches used as experimental models to study fibromyalgia, type II diabetes mellitus, and soreness induced by unaccustomed eccentric exercise, respectively. SIGNIFICANCE We demonstrated that the profile of PORH in the anterior tibialis muscle of rats is sensitive to a variety of experimental models often associated with the skeletal muscle functionality, providing a useful strategy to explore how and whether changes in local regulation of blood flow can contribute to the development of skeletal muscle associated symptoms in clinically relevant conditions.

Molecular Neurobiology, 2020

Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly cha... more Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including alterations in adenosine neuromodulation. The administration of caffeine (a non-selective adenosine receptor antagonist) and physical exercise have been independently pointed as effective approaches for the management of ADHD symptoms. Here, we evaluated the effects of caffeine consumption (0.3 mg/mL in drinking water) plus physical exercise in running wheels during 6 weeks—starting during either adolescence (30 days old) or adulthood (4–5 months old)—on behavioral performance (including olfactory discrimination, open field, object recognition, and water maze tests) on the brain levels of monoamines (by high-performance liquid chromatography), on proteins related to synaptic plasticity and on brain-derived neurotrophic factor signaling (by Western blot analysis) in spontaneously hypertensive rats (SHRs), a validated animal model of ADHD. SHRs displayed persistent impairments of olfactory and short-term recognition memory from adolescence to adulthood, which were accompanied by lower levels of synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex and hippocampus. The association of caffeine plus physical exercise during adolescence or adulthood restored the olfactory discrimination ability and, in an independent manner, improved short-term recognition memory of SHRs. These benefits were not associated to alterations in locomotor activity or in the hypertensive phenotype. The association of caffeine consumption plus physical exercise during adolescence increased the levels of SNAP-25, syntaxin, and serotonin in the hippocampus and prefrontal cortex, and striatal dopamine levels in SHRs. These results provide new evidence of the potential of caffeine and physical exercise, starting at adolescence or adult life, to improve behavioral impairments and stimulate neuroplasticity in ADHD.

Food Research International, 2020

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial-ShareAlike| 4.0 International License

American Journal of Hypertension, 2019

BACKGROUND This study was designed to evaluate whether overconsumption of NaCl, a well-known risk... more BACKGROUND This study was designed to evaluate whether overconsumption of NaCl, a well-known risk factor for hypertension, leads to erectile dysfunction in rodents. METHODS Male Wistar rats received regular chow (control group) or 4% NaCl chow for 24 weeks and were subjected to blood pressure measurement and apomorphine-induced erection. Moreover, cavernosal strips from both the control and 4% NaCl groups were evaluated in organ baths. RESULTS Animals subjected to 4% NaCl chow did not develop hypertension but presented a significant reduction in the total number of erections following apomorphine administration as compared with the control group. The addition of high KCl or phenylephrine resulted in similar contractile responses in the corpus cavernosal strips from both the control and 4% NaCl groups. However, electrical field stimulation-induced contraction was significantly enhanced in cavernosal strips from animals exposed to 4% NaCl. Incubation of Y-27632, but not of atropine an...