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The synthetic nitro-alcohol 2-nitro-1-phenyl-1-propanol (NPP) has endothelium-independent relaxing properties in isolated preparations of rat aorta and mesenteric artery. In this study, we investigated whether the vasodilator effects occur in coronary vessels and explored whether hyperpolarization is involved in the underlying mechanism of NPP-induced smooth muscle relaxation. The relaxing responses were studied in isolated preparations of the left anterior descending coronary (ADC) and the septal coronary (SC) arteries, which had been previously maintained under sustained contraction induced by the thromboxane A2 analogue U-46619. Administered cumulatively, NPP elicited concentration-dependent vasorelaxation with similar potency in both vessels. The relaxant effect remained unaffected by the nitric oxide synthase inhibitor L-NAME, the protein kinase C inhibitor bisindolylmaleimide IV and the Rho-associated protein kinase inhibitor Y-27632. However, it was significantly diminished by the adenylyl cyclase inhibitor MDL-12,330A, the guanylyl cyclase inhibitor ODQ, as well as the K+ channel inhibitors tetraethylammonium and CsCl. In ADC preparations impaled with intracellular micropipettes, NPP hyperpolarized the vascular preparation. When the isolated preparation was precontracted by 5-hydroxytryptamine or 80 mM KCl, NPP-induced relaxation with lower pharmacological potency compared to the vessels contracted by U-46619. In conclusion, NPP exhibits vasorelaxant effects on rat coronary arteries, likely involving pathways that include cyclic nucleotide production and membrane hyperpolarization.
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BACKGROUND & AIMS: Changes in dietary habits including increased intake of refined sugars and fats and decreased intake of fiber have been suggested as potential risk factors for the development of inflammatory bowel diseases (IBD). Bioelectrical impedance analysis-derived phase angle (PhA) has been gaining attention in the clinical evaluation of nutritional status. In this study, we for the first time investigated the relationship of PhA and ultra-processed food intake with oxidative stress, body composition and biochemical parameters in adult patients with IBD. METHODS: Body composition and PhA were evaluated through electrical bioimpedance. Nitrite (Nox), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in both groups. Food consumption was obtained by a food frequency questionnaire (FFQ). RESULTS: In comparison with the control group, the IBD group had increased (p < 0.05) concentrations of Nox (19.95 ± 1.4 vs. 35.43 ± 7.7 µM), MDA (0.70 ± 0.31 vs. 4.56 ± 0.62 nmol/L), and GSH (9.35 ± 0.38 vs. 10.74 ± 0.51 mg NPSH/µL plasma). PhA was positively correlated with GSH (R2:0.22; p:0.02) and SOD (R2:0.25; p:0.01). IBD patients ingested higher amounts of ultra-processed foods (IBD:17.04 ± 2.76 vs. Control:24.88 ± 2.30%). However, IBD patients had better consumption of unprocessed or minimally processed foods (IBD:79.06 ± 3.07 vs. Control:67.83 ± 2.32%). We found a positive correlation between ultra-processed food consumption and MDA (R2 0.43; p:0.01). CONCLUSIONS: PhA may be a practical and effective measure in clinical follow-up of IBD patients, being associated with bilirubin levels and antioxidant enzymes. Also, we recommend evaluating consumption of ultra-processed foods, since this was related with increasing oxidative stress markers in clinical follow-up of IBD patients.
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Alimentos Procesados , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Estrés Oxidativo , Antioxidantes , Composición Corporal , GlutatiónRESUMEN
AIM: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder in women. We investigate the effect of physical exercise on body composition, nutritional parameters, and oxidative stress in rats with PCOS. METHODS: Female rats were into three groups: Control, PCOS, and PCOS + Exercise. PCOS was induced by letrozole (1 mg/kg via p.o.) for 21 days consecutively. Physical exercise was swimming, for 21 consecutive days, 1 h/day with 5 % load. In all groups, we assessed the nutritional and murinometric parameters, body composition, thermography, and oxidative stress in brown adipose tissue (BAT) and peri-ovarian adipose tissue (POAT). KEY FINDINGS: In PCOS we observed an increase (P < 0.05) in body weight vs. the Control group. But, the PCOS + Exercise group prevent this weight gain (P < 0.05). The temperature in BAT, decrease (P < 0.05) in the PCOS group vs. Control group. PCOS + Exercise prevented this reduction (P < 0.05) in BAT temperature vs. PCOS groups. We observed decreases (P < 0.05) in Lee Index and BMI in POS + Exercise vs. PCOS group. In PCOS rats, we observed an increase (P < 0.05) in murinometric (SRWG, EI, and FE) and body composition parameters (TWB, ECF, ICF, and FFM) vs. the Control group. The PCOS + Exercise prevents (P < 0.05) these changes in all groups, compared with PCOS. Regarding the BAT, we observe an increase (P < 0.05) in MPO and MDA levels in the PCOS vs. Control group. PCOS + Exercise prevents (P < 0.05) these increases vs. the PCOS group. SIGNIFICANCE: PCOS modifies body composition, and nutritional parameters, and induces changes in oxidative stress in BAT. Physical exercise prevented these alterations.
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Tejido Adiposo Pardo , Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratas , Animales , Síndrome del Ovario Poliquístico/terapia , Síndrome del Ovario Poliquístico/inducido químicamente , Composición Corporal , Peso Corporal , Estrés OxidativoRESUMEN
Few studies have focused on nutrient-deficient diets and associated pathobiological dynamics of body composition and intestinal barrier function. This study evaluated the impact of a nutrient-deficient diet on physical development and intestinal morphofunctional barrier in mice. C57BL/6 (21 days of age) mice were fed a Northeastern Brazil regional basic diet (RBD) or a control diet for 21 d. The animals were subjected to bioimpedance analysis, lactulose test, morphometric analysis and quantitative reverse transcription-PCR to evaluate tight junctions and intestinal transporters. RBD feeding significantly reduced weight (P < 0·05) from day 5, weight gain from day 3 and tail length from day 14. The intake of RBD reduced total body water, extracellular fluid, fat mass and fat-free mass from day 7 (P < 0·05). RBD induced changes in the jejunum, with an increase in the villus:crypt ratio on day 7, followed by reduction on days 14 and 21 (P < 0·05). Lactulose:mannitol ratio increased on day 14 (P < 0·05). Changes in intestinal barrier function on day 14 were associated with reductions in claudin-1 and occludin, and on day 21, there was a reduction in the levels of claudin-2 and occludin. SGLT-1 levels decreased on day 21. RBD compromises body composition and physical development with dynamic changes in intestinal barrier morphofunctional. RBD is associated with damage to intestinal permeability, reduced levels of claudin-1 and occludin transcripts and return of bowel function in a chronic period.
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Dieta , Lactulosa , Ratones , Animales , Ocludina/genética , Claudina-1/genética , Claudina-1/metabolismo , Destete , Lactulosa/metabolismo , Ratones Endogámicos C57BL , Mucosa Intestinal/metabolismo , Composición CorporalAsunto(s)
Pan , Enfermedades Inflamatorias del Intestino , Fibras de la Dieta , Humanos , Secale , TriticumRESUMEN
Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR1a, ATR1b, and ATR2. We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats. Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1ß, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR1A, ATR1B, and ATR2). Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased (p<0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower (p<0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher (p<0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower (p<0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher (p<0.05) gene expression of ATR2 in the duodenum. Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise.
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This study tested the effects of ß-methylphenylethylamine (ß-MPEA) and octopamine on contractile parameters of the gastrointestinal tract in rats. We hypothesized that some of their effects result from interactions with trace amine (TA)-associated receptors or serotoninergic 5-hydroxytryptamine (5-HT) receptors. ß-MPEA-induced contractions in rat gastric fundus strips under resting tonus conditions, but induced relaxation in preparations that were previously contracted with carbachol. Octopamine relaxed gastric fundus strips maintained at resting tonus or contracted with carbachol. The contractile effect of ß-MPEA was reduced by cyproheptadine and methiothepin, antagonists of excitatory 5-HT receptors. The relaxing effect of ß-MPEA on gastric fundus was insensitive to pretreatment with N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl)benzamide (EPPTB) and tropisetron, antagonists of TA1 and 5-HT4 receptors, respectively. Both EPPTB and tropisetron inhibited the relaxant effects of octopamine on carbachol-contracted preparations. Contrarily, EPPTB did not reduce the relaxant effects of RO5263397 (TA1 agonist) or zacopride (5-HT4 agonist). Octopamine, but not ß-MPEA, delayed the gastrointestinal transit of a liquid test meal in awaken rats. In isolated preparations of the small intestine under resting conditions, ß-MPEA did not alter the basal tonus, but octopamine relaxed it. Intestinal preparations previously contracted with carbachol relaxed after the addition of octopamine and decreased the magnitude of their spontaneous rhythmic contractions in a tropisetron-dependent manner. Thus, ß-MPEA and octopamine exerted pharmacological actions on the rat gastrointestinal tract. The excitatory effects of ß-MPEA involved 5-HT receptors. Octopamine inhibited the rat gut contractility through the likely involvement of 5-HT4 and TA receptors. Overall, octopamine effectively inhibited rat gastrointestinal transit.
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Anfetaminas , Octopamina , Animales , Fundus Gástrico , Contracción Muscular , Relajación Muscular , Músculo Liso , Ratas , Receptores de SerotoninaRESUMEN
AIMS: We examined the effects of treatment with 1-nitro-2-phenylethane (NP), a novel soluble guanylate cyclase stimulator, on monocrotaline (MCT)-induced PAH in rats. MAIN METHODS: At day 0, male adult rats were injected with a single subcutaneous (s.c.) dose of monocrotaline (60 mg/kg). Control (CNT) rats received an equal volume of monocrotaline's vehicle only (s.c.). Four weeks later, MCT-treated rats were treated orally for 14 days with NP (50 mg/kg/day) (MCT-NP group) or its vehicle (Tween 2%) (MCT-V group). At the end of the treatment period and before invasive hemodynamic study, rats of all experimental groups were examined by echocardiography. KEY FINDINGS: With respect to CNT rats, MCT-V rats showed significant; (1) increases in pulmonary artery (PA) diameter, RV free wall thickness and end-diastolic RV area, and increase of Fulton index; (2) decreases in maximum pulmonary flow velocity, PA acceleration time (PAAT), PAAT/time of ejection ratio, and velocity-time integral; (3) increases in estimated mean pulmonary arterial pressure; (4) reduction of maximal relaxation to acetylcholine in aortic rings, and (5) increases in wall thickness of pulmonary arterioles. All these measured parameters were significantly reduced or even abolished by oral treatment with NP. SIGNIFICANCE: NP reversed endothelial dysfunction and pulmonary vascular remodeling, which in turn reduced ventricular hypertrophy. NP reduced pulmonary artery stiffness, normalized the pulmonary artery diameter and alleviated RV enlargement. Thus, NP may represent a new therapeutic or a complementary approach to treatment of PAH.
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Derivados del Benceno/farmacología , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Animales , Ecocardiografía , Endotelio Vascular/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Masculino , Monocrotalina/antagonistas & inhibidores , Monocrotalina/farmacología , Hipertensión Arterial Pulmonar/inducido químicamente , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Arteria Pulmonar/efectos de los fármacos , Ratas , Ratas Wistar , Guanilil Ciclasa Soluble/efectos de los fármacos , Remodelación Vascular/efectos de los fármacosRESUMEN
CONTEXT: Glutamine supplementation has been applied clinical practice to treat inflammatory bowel disease (IBD). However, scientific evidence about this is still controversial. OBJECTIVE: In this review, we systematically evaluated the effects of glutamine supplementation on IBD, based on evidence from randomized clinical trials. DATA SOURCE: This review was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We used the PubMed and SciVerse Scopus databases. The Cochrane collaboration tool was used to assess the risk of bias in clinical trials. DATA EXTRACTION: The review was carried out by two independent researchers according to the established inclusion criteria. The PICO (patient, intervention, comparison, and outcomes) strategy was used, with the descriptors: "glutamine," "supplementation," "inflammatory bowel diseases," "Crohn's disease," and "ulcerative colitis". DATA SYNTHESIS: Seven research articles were selected for this systematic review. In these studies, glutamine was administered to the participants through oral (21-30g or 0.5g per kg of participant's body weight), enteral (7.87g-8.3 g/100g of the enteral formula), and/or parenteral (0.3 g/kg of the participant's body weight) routes. No changes in anthropometry or biochemical parameters were observed. However, in one study reduced intestinal permeability and morphometry were reported. In two other studies, a slight effect of glutamine on inflammation and oxidative stress was observed. Additionally, two other studies reported an effect of glutamine supplementation on disease activity. CONCLUSIONS: The findings obtained through this systematic review indicate that glutamine supplementation has no effect on disease course, anthropometric measurements, intestinal permeability and morphology, disease activity, intestinal symptoms, biochemical parameters, oxidative stress and inflammation markers in patients with IBD, regardless of the route of administration, either treated at a hospital or as outpatients.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Ensayos Clínicos como Asunto , Suplementos Dietéticos , Glutamina , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológicoRESUMEN
Cisplatin treatment induces an autonomic dysfunction and gastrointestinal and cardiovascular disorders. Physical exercise as well as pyridostigmine treatment induces improves in the autonomic nervous system. In the current study, we investigated the effect of physical exercise and pyridostigmine treatment on gastrointestinal and cardiovascular changes in cisplatin-treated rats. Rats were divided into groups: Saline (S), Cisplatin (Cis), Exercise (Ex), Cisplatin+Exercise (Cis+Ex), Pyridostigmine (Pyr), and Cisplatin+Pyridostigmine (Cis+Pyr). We induced gastrointestinal dysmotility by administering 3 mg kg-1 of cisplatin once week for 5 weeks. The Ex was swimming (1 h per day/5 days per week for 5 weeks with 5% b.w.). GE was evaluated through the colorimetric method of fractional red phenol recovery 10 min after feeding. Pyr groups received 1.5 mg kg-1, p.o. or concomitant Cis treatment. Moreover, gastric contraction in vitro and hemodynamic parameters such as MAP, HR, and evoked baroreflex sensitivity were assessed, as well as sympathetic and parasympathetic tone and intrinsic heart rate (IHR). Cis decrease GE vs. saline (p<0.05). Cis+Ex or Cis+Pyr prevented (p<0.05) decrease in GE vs. Cis rats. Cis decreased (p<0.05) gastric responsiveness in vitro vs. saline. Cis+Ex or Cis+Pyr prevented this phenomenon. Cis treatment increase MAP and decrease in HR (p<0.05) vs saline. Cis+Ex or Cis+Pyr attenuated (p<0.05) both alterations. Cis increased sympathetic tone and decreased vagal tone and IHR (p<0.05) vs. the saline. Cis+Ex or Cis+Pyr prevented those effects vs. the Cis group. In conclusion, physical exercise and pyridostigmine treatment improves autonomic dysfunction and prevented GE delay and changes in hemodynamic parameters, baroreflex sensitivity, and cardiac autonomic control in cisplatin-treated rats.
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Barorreflejo/efectos de los fármacos , Condicionamiento Físico Animal/fisiología , Bromuro de Piridostigmina/farmacología , Animales , Sistema Nervioso Autónomo/fisiopatología , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Sistema Cardiovascular/fisiopatología , Cisplatino/efectos adversos , Cisplatino/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Infarto del Miocardio/fisiopatología , Ratas , Ratas Wistar , Nervio Vago/efectos de los fármacosRESUMEN
The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1ß, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1ß, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.
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Colitis Ulcerosa/terapia , Fármacos Gastrointestinales/uso terapéutico , Motilidad Gastrointestinal/efectos de los fármacos , Glutamina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Condicionamiento Físico Animal/métodos , Administración Oral , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Biomarcadores/metabolismo , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colitis Ulcerosa/fisiopatología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Terapia Combinada , Citocinas/metabolismo , Suplementos Dietéticos , Esquema de Medicación , Fármacos Gastrointestinales/farmacología , Motilidad Gastrointestinal/fisiología , Glutamina/farmacología , Masculino , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos , Pérdida de Peso/fisiologíaRESUMEN
The aim of this study was to investigate the effect of cachexia induced by AH-130 cells on gastrointestinal motility in rats. We evaluated food intake, body weight variation, cachexia index, gastric emptying and in vitro gastric responsiveness of control or cachexia rats. In addition, we evaluated the effect of pretreatment with atenolol (20 mg/kg, p.o.), win 55,212-2 (2 mg/kg, s.c.) or subdiaphragmatic vagotomy on the effects found. Atenolol prevented (P < 0.05) the acceleration of gastric emptying (area under the curve, AUC, 20360.17 ± 1970.9 vs. 12579.2 ± 785.4 µg/min/ml), and increased gastric responsiveness to carbachol (CCh) stimulation in cachectic rats compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 46.5 ± 5.7%). Vagotomy prevented (P < 0.05) increase in gastric emptying acceleration (AUC 20360.17 ± 1970.9 vs. 13414.0 ± 1112.9 µg/min/ml) and caused greater in vitro gastric responsiveness of cachectic compared to control rats (CCh-6M: 63.2 ± 5.5% vs. 31.2 ± 4.7%). Win 55,212-2 attenuated the cachexia index (38.5 ± 2.1% vs. 25.8 ± 2.7%), as well as significantly (P < 0.05) preventing increase in gastric emptying (AUC 20360.17 ± 1970.9 vs. 10965.4 ± 1392.3 µg/min/ml) and gastric responsiveness compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 38.2 ± 3.9%). Cachexia accelerated gastric emptying and increased gastric responsiveness in vitro. These phenomena were prevented by subdiaphragmatic vagotomy and by atenolol and win 55,212-2 treatments, showing vagal involvement of ß1-adrenergic and cannabinoid CB1/CB2 receptors.
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Atenolol/farmacología , Benzoxazinas/farmacología , Caquexia/patología , Caquexia/fisiopatología , Vaciamiento Gástrico/efectos de los fármacos , Morfolinas/farmacología , Naftalenos/farmacología , Vagotomía , Animales , Línea Celular Tumoral , Endocannabinoides/metabolismo , Masculino , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/metabolismo , Receptores de Cannabinoides/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Neryl butyrate is a constituent of volatile oils obtained from aromatic plants. Aliphatic organic compound analogues chemically close to neryl butyrate possess vasodilator properties in rat aorta. To evaluate whether neryl butyrate has relaxing properties, this study tested its effects on isolated rat aorta. Unlike the analogues, neryl butyrate did not show relaxant profile in aortic rings precontracted with phenylephrine, but induced a contraction when it stimulated aortic rings under resting tonus. The contractile effect augmented in endothelium-denuded aortic rings. Treatment of endothelium-intact preparations with the nitric oxide synthase inhibitor L-NAME or the guanylyl cyclase inhibitor ODQ also augmented the contractile effect of neryl butyrate. Such phenomenon was absent in the presence of the cyclooxygenase inhibitor indomethacin. Contractile responses decreased in the presence of verapamil, a L-type Ca2+ channel blocker, or when Ca2+ was removed from the extracellular solution. Antagonists of α-adrenergic receptors (prazosin and yohimbine), but not the thromboxane-prostanoid receptor seratrodast, reversed the contraction induced by neryl butyrate. The α1A selective antagonist RS-17053 antagonized the neryl butyrate-induced contraction. The contraction caused by neryl butyrate was decreased by inhibiting the phospholipase C or the rho-associated kinase with U-73122 or Y-27632, respectively. Injected intravenously to awake rats, neryl butyrate induced arterial hypotension and bradycardia. Decreased frequency was also present in isolated right atrium preparations. In conclusion, the contractile effects of neryl butyrate were inhibited by α-adrenergic antagonists, indicating the involvement of α-adrenoceptors in the mechanism of action. In vivo, neryl butyrate caused hypotension, suggesting that other systemic influence than vasoconstriction may occur.
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Aorta Torácica/efectos de los fármacos , Butiratos/farmacología , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Agonistas alfa-Adrenérgicos/farmacología , Amidas/farmacología , Animales , Aorta Torácica/fisiología , Calcio/farmacología , Estrenos/farmacología , Atrios Cardíacos/efectos de los fármacos , Técnicas In Vitro , Masculino , Fenilefrina/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Pirrolidinonas/farmacología , Ratas WistarRESUMEN
The chronic use of Dexamethasone (Dex) induced hyperglycemia and insulin resistance. On the other hand, physical exercise attenuates the symptoms induced by Dex in many physiological systems. However, the effect of the exercise on the changes in gastric motility induced by dexamethasone remains unknown. We hypothesized that low-intensity aerobic exercise modulates the metabolic effects induced by Dex-treatment by modifying the gastrointestinal function and feeding behavior in rats. Male rats were distributed into the following groups: Control (Ctrl), Dex (1.0â¯mg/kg, i.p.), Exercise (Ctrlâ¯+â¯Exercise 5%) and (Dex1.0â¯+â¯Exercise 5%). The exercise protocol was swimming for 5 consecutive days. We assessed the murinometric and nutritional indices, food intake, blood glucose by (ipGTT) and the gastric emptying rate of a liquid test meal were assessed in all rats. We observed a significant decrease (pâ¯<â¯.05) in the gastric emptying in Dex1.0â¯group in relation to Ctrl group. The exercise prevented decrease in the gastric emptying (pâ¯<â¯.05) in Dex1.0â¯+â¯EX5% group when compared with Dex1.0â¯groups. The Dex1.0â¯group induced a significantly increase (pâ¯<â¯.05) in glycaemia vs Ctrl group. The hyperglycemia was improving (pâ¯<â¯.05) in the Dex1.0â¯+â¯Ex5% compared with Dex1.0â¯groups. We observed a positive correlation (pâ¯<â¯.05, and râ¯=â¯0.7065) between gastric retention vs glycaemia in the Dex1.0â¯groups. The Dex1.0 reduced (pâ¯<â¯.05) the body weight and altered body composition, promoting hypophagia. IL-6 increased (pâ¯<â¯.05) at gastric fundus in Ex5% compared with Ctrl groups. In conclusion, the use of Dex1.0 decreases gastric emptying, promotes hyperglycemia and modifies feeding behavior. The low-intensity exercise prevents hyperglycemia, thus improving gastric dysmotility without improving the anthropometric parameters.
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Apetito/efectos de los fármacos , Apetito/fisiología , Dexametasona/farmacología , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Condicionamiento Físico Animal/psicología , Animales , Glucemia/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Citocinas/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Natación/psicologíaRESUMEN
Actually, arterial hypertension is a major public health concern, which involves the renin angiotensin aldosterone system (RAS), via activation of the angiotensin receptors AT1 and AT2 of the cardiovascular system. Although angiotensin is an important stimulant of the gut permeability to sodium and water, little is known about the effects of arterial hypertension on gut motor behavior. Thus, we evaluated in rats the effect of hypertension induced by two-kidney one-clip (2K1C) model on the gastric motility, as well as the influence of exercise and RAS blockers treatment in such phenomenon. One week after surgery the rats were treated with Aliskiren (50â¯mg·kg-1, p.o.), Captopril (50â¯mg·kg-1, p.o.) or Losartan (10â¯mg·kg-1, p.o). Other group of rats was submitted to swimming with 5% body weight overload. After 4â¯weeks of physical training or pharmacological treatment, we assessed the gastric retention in all groups (GR) of a liquid test meal, the mean arterial pressure (MAP), the heart rate (HR) and the HR variation (HRV) as well as the in vitro contractility of gastric fundus. Renovascular hypertension increased (pâ¯<â¯0.05) the GR, MAP and HR, a phenomenon prevented by pretreatment with RAS blockers or exercise. The two kidney one-clip Hypertension (2K1C) decreased (pâ¯<â¯0.05) the gastric fundus responsiveness, a phenomenon also prevented by exercise. It conclusion, renovascular hypertension delays the gastric emptying of liquids, a phenomenon involving the activation of RAS, where exercise or blockade with aliskiren, captopril and losartan prevent gastric dysmotility.
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Antihipertensivos/farmacología , Vaciamiento Gástrico/fisiología , Gastroparesia/terapia , Hipertensión Renovascular/complicaciones , Condicionamiento Físico Animal , Sistema Renina-Angiotensina/efectos de los fármacos , Angiotensina II/metabolismo , Animales , Terapia Combinada , Vaciamiento Gástrico/efectos de los fármacos , Gastroparesia/etiología , Gastroparesia/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1ß, and transforming growth factor-ß. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols. 1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.
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Lesión Renal Aguda/prevención & control , Catecoles/administración & dosificación , Alcoholes Grasos/administración & dosificación , Peritonitis/complicaciones , Sepsis/complicaciones , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/mortalidad , Animales , Dimetilsulfóxido/metabolismo , Dimetilaminas/metabolismo , Modelos Animales de Enfermedad , Heces/microbiología , Humanos , Inyecciones Intraperitoneales , Masculino , Metaboloma/efectos de los fármacos , Metabolómica , Estrés Oxidativo/efectos de los fármacos , Peritonitis/metabolismo , Peritonitis/microbiología , Peritonitis/mortalidad , Ratas , Ratas Wistar , Sepsis/metabolismo , Sepsis/microbiología , Sepsis/mortalidad , Sulfonas/metabolismo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
NEW FINDINGS: What is the central question of this study? Acute acidosis that results from short-term exercise is involved in delayed gastric emptying in rats and the lower responsiveness of gastric fundus strips to carbachol. Does extracellular acidosis decrease responsiveness to carbachol in tissues of sedentary rats? How? What is the main finding and its importance? Extracellular acidosis inhibits cholinergic signalling in the rat gastric fundus by selectively influencing the Gq/11 protein signalling pathway. Acute acidosis that results from short-term exercise delays gastric emptying in rats and decreases the responsiveness to carbachol in gastric fundus strips. The regulation of cytosolic Ca2+ concentrations appears to be a mechanism of action of acidosis. The present study investigated the way in which acidosis interferes with gastric smooth muscle contractions. Rat gastric fundus isolated strips at pH 6.0 presented a lower magnitude of carbachol-induced contractions compared with preparations at pH 7.4. This lower magnitude was absent in carbachol-stimulated duodenum and KCl-stimulated gastric fundus strips. In Ca2+ -free conditions, repeated contractions that were induced by carbachol progressively decreased, with no influence of extracellular pH. In fundus strips, CaCl2 -induced contractions were lower at pH 6.0 than at pH 7.4 but only when stimulated in the combined presence of carbachol and verapamil. In contrast, verapamil-sensitive contractions that were induced by CaCl2 in the presence of KCl did not change with pH acidification. In Ca2+ store-depleted preparations that were treated with thapsigargin, the contractions that were induced by extracellular Ca2+ restoration were smaller at pH 6.0 than at pH 7.4, but relaxation that was induced by SKF-96365 (an inhibitor of store-operated Ca2+ entry) was unaltered by extracellular acidification. At pH 6.0, the phospholipase C inhibitor U-73122 relaxed carbachol-induced contractions less than at pH 7.4, and this phenomenon was absent in tissue that was treated with the RhoA kinase blocker Y-27632. Thus, extracellular acidosis inhibited pharmacomechanical coupling in gastric fundus by selectively inhibiting the Gq/11 protein signalling pathway, whereas electromechanical coupling remained functionally preserved.
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Acidosis/metabolismo , Señalización del Calcio/efectos de los fármacos , Carbacol/farmacología , Agonistas Colinérgicos/farmacología , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Fundus Gástrico/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Fundus Gástrico/metabolismo , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Masculino , Músculo Liso/metabolismo , Ratas WistarRESUMEN
α-Terpineol is a monoterpene with smooth muscle relaxant properties. In this study, its effects on the gastric emptying rate of awake rats were evaluated with emphasis on the mode by which it induces gastrointestinal actions. Administered by gavage, α-terpineol (50 mg/kg) delayed gastric emptying of a liquid test meal at 10 min postprandial. Hexamethonium or guanethidine did not interfere with the retarding effect induced by α-terpineol, but atropine and L-NG-nitroarginine methyl ester abolished it. In vagotomized rats, α-terpineol did not delay gastric emptying. In isolated strips of gastric fundus, concentration-effect curves in response to carbamylcholine were higher in magnitude after treatment with the monoterpene. α-Terpineol (1 to 2000 µM) relaxed sustained contractions induced by carbamylcholine or a high K+ concentration in a concentration-dependent manner. This relaxing effect was not affected by the presence of L-NG-nitroarginine methyl ester, 1 H-[1,â2,â4]oxadiazolo[4,3-a]quinoxalin-1-one, tetraethylammonium, or atropine. Smooth muscle contractions induced by electrical field stimulation were inhibited by α-terpineol. In conclusion, α-terpineol induced gastric retention in awake rats through mechanisms that depended on intact vagal innervation to the stomach, which involved cholinergic/nitrergic signalling. Such a retarding effect induced by α-terpineol appears not to result from a direct action of the monoterpene on gastric smooth muscle cells.
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Ciclohexenos/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Fundus Gástrico/efectos de los fármacos , Monoterpenos/farmacología , Nervio Vago/efectos de los fármacos , Animales , Atropina/farmacología , Carbacol/farmacología , Monoterpenos Ciclohexánicos , Ciclohexenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Vaciamiento Gástrico/fisiología , Guanetidina/farmacología , Masculino , Monoterpenos/administración & dosificación , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Técnicas de Cultivo de Órganos , Potasio/farmacología , Ratas Wistar , Simpaticolíticos/farmacología , Vagotomía , Nervio Vago/metabolismo , Nervio Vago/cirugíaRESUMEN
ß-Citronellol is a monoterpene found in the essential oil of various plants with antihypertensive properties. In fact, ß-citronellol possesses hypotensive actions due to its vasodilator abilities. Here we aimed to show that ß-citronellol recruits airway sensory neural circuitry to evoke cardiorespiratory effects. In anesthetized rats, intravenous injection of ß-citronellol caused biphasic hypotension, bradycardia and apnea. Bilateral vagotomy, perivagal capsaicin treatment or injection into the left ventricle abolished first rapid phase (named P1) but not delayed phase P2 of the ß-citronellol effects. P1 persisted after pretreatment with capsazepine, ondansetron, HC-030031 or suramin. Suramin abolished P2 of apnea. In awake rats, ß-citronellol induced biphasic hypotension and bradycardia being P1 abolished by methylatropine. In vitro, ß-citronellol inhibited spontaneous or electrically-evoked contractions of rat isolated right or left atrium, respectively, and fully relaxed sustained contractions of phenylephrine in mesenteric artery rings. In conclusion, chemosensitive pulmonary vagal afferent fibers appear to mediate the cardiovascular and respiratory effects of ß-citronellol. The transduction mechanism in P1 seems not to involve the activation of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential ankyrin subtype 1 (TRPA1), purinergic (P2X) or 5-HT3 receptors located on airways sensory nerves. P2 of hypotension and bradycardia seems resulting from a cardioinhibitory and vasodilatory effect of ß-citronellol and the apnea from a purinergic signaling.
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Apnea/inducido químicamente , Bradicardia/inducido químicamente , Hipotensión/inducido químicamente , Monoterpenos/farmacología , Monoterpenos Acíclicos , Animales , Apnea/fisiopatología , Presión Arterial/efectos de los fármacos , Función Atrial/efectos de los fármacos , Bradicardia/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hipotensión/fisiopatología , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/fisiología , Ratas Wistar , Frecuencia Respiratoria/efectos de los fármacos , Vagotomía , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiologíaRESUMEN
AIMS: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury. MAIN METHODS: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9). KEY FINDINGS: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury. SIGNIFICANCE: Acute ischemic kidney injury is exacerbated by acidic conditions.