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1.
J. physiol. biochem ; 78(4): 753–762, nov. 2022. graf
Artigo em Inglês | IBECS | ID: ibc-216169

RESUMO

The involvement of renin-angiotensin system in the modulation of gut motility and age-related changes in mRNA expression of angiotensin (Ang II) receptors (ATR) are well accepted. We aimed to characterize, in vitro, the contractile responses induced by Ang II, in jejunum from young (3–6 weeks old) and old rats (≥ 1 year old), to evaluate possible functional differences associated to changes in receptor expression. Mechanical responses to Ang II were examined in vitro as changes in isometric tension. ATR expression was assessed by qRT-PCR. Ang II induced a contractile effect, antagonized by losartan, AT1R antagonist, and increased by PD123319, AT2R antagonist, as well by neural blocker ω-conotoxin and by nitric oxide (NO) synthase inhibitor. No difference in the response was observed between young and old groups. AT1 receptor-mediated contractile response was decreased by U-73122, phospholipase C (PLC) inhibitor; or 2-aminoethoxy-diphenylborate (2-APB), inositol triphosphate (IP3) receptor inhibitor; or nifedipine, L-type calcium channel blocker. Age-related changes in the expression of both AT1 receptor subtypes, AT1a and AT1b, and of AT2 receptors were detected. In conclusion, Ang II modulates the spontaneous contractility of rat jejunum via postjunctional AT1 receptors, involving Ca2+ mobilization from intracellular stores, via PLC/IP3 pathway, and Ca2+ influx from extracellular space, via L-type channels. Prejunctional AT2 receptors would counteract AT1 receptor effects, via NO synthesis. The observed age-related differences in the expression of all AT receptor subtypes are not reflected in the muscular contractile response to Ang II. (AU)


Assuntos
Animais , Ratos , Receptor Tipo 1 de Angiotensina/genética , Angiotensina II/farmacologia , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo , Jejuno/metabolismo , Losartan/farmacologia , Envelhecimento
2.
J. physiol. biochem ; 78(1): 245-256, feb. 2022.
Artigo em Inglês | IBECS | ID: ibc-215886

RESUMO

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, and the dysregulated circular RNAs (circRNAs) play key roles in AAA progression. Circ_0092291 was downregulated in AAA patients, but its function in AAA remains unclear. This research was performed for the functional analysis of circ_0092291 and its mechanism exploration with mircoRNA-626 (miR-626) and collagen type IV alpha1 chain (COL4A1) in AAA. Human aortic vascular smooth muscle cells (T/G HA-VSMC) were treated with angiotensin II (Ang II). Levels of circ_0092291, miR-626, and COL4A1 were determined using reverse transcription–quantitative polymerase chain reaction (RT-qPCR). Inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was measured using caspase3 activity assay and flow cytometry. Angiopoiesis was assessed via tube formation assay. The protein analysis was conducted by western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to validate the molecular binding. Circ_0092291 downregulation was found in AAA samples and Ang II-treated cells. Inflammatory response and cell apoptosis were reduced while angiopoiesis and ECM level were facilitated after overexpression of circ_0092291 in Ang II-treated T/G HA-VSMC cells. MiR-626 was a miRNA target for circ_0092291, and miR-626 inhibition protected T/G HA-VSMC from Ang II–induced cell injury. Moreover, the regulation of circ_0092291 was achieved by serving as a miR-626 sponge in Ang II-treated cells. COL4A1 was affirmed as a target for miR-626 and circ_0092291 resulted in the level change of COL4A1 by sponging miR-626. Additionally, miR-626 downregulation inhibited the cell damages caused by Ang II through increasing the level of COL4A1 and the function of circ_0092291 was attributed to the upregulation of COL4A1. (AU)


Assuntos
Humanos , Angiotensina II/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Colágeno Tipo IV/metabolismo , RNA
3.
J. physiol. biochem ; 78(1): 257-269, feb. 2022.
Artigo em Inglês | IBECS | ID: ibc-215887

RESUMO

Hypertension or angiotensin II (Ang II) induces cardiac inflammation and fibrosis, thus contributing to cardiac remodeling. MicroRNAs (miRNAs) are considered crucial regulators of cardiac homeostasis and remodeling in response to various types of stress. It has been reported that miR-451a is involved in regulating ischemic heart injury. However, its role in Ang II-induced cardiac fibrosis remains unknown. Cardiac remodeling was induced in mice by infusion of low-dose Ang II (490 ng/kg/min) with a minipump for 2 weeks. Echocardiography and histological examinations were performed to evaluate cardiac function and pathological changes. We observed that miR-451a expression was the most significantly downregulated in the hearts of Ang II-infused mice and in both primary cardiac myocytes and fibroblasts. Overexpression of miR-451a in mice significantly attenuated Ang II–induced cardiac fibrosis and inflammation. Conversely, knockdown of miR-451a in mice aggravated this effect. Bioinformatics analysis and a luciferase reporter assay revealed that TBX1 was a direct target of miR-451a. Mechanistically, miR-451a directly targeted TBX1 expression, which inhibited TGF-β1 production in both cardiac myocytes and fibroblasts, inactivating of TGF-β1/SMAD2/3 signaling, inhibiting myofibroblast differentiation and proinflammatory cytokine expression, and leading to attenuation of cardiac fibrosis and inflammation. In conclusion, these results indicate that miR-451a acts as a novel regulator of Ang II–induced cardiac fibrosis and inflammation by directly targeting TBX1, and may be a promising therapeutic target for treating hypertensive cardiac diseases. (AU)


Assuntos
Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Angiotensina II/metabolismo , Fibrose , Inflamação , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo
5.
Nefrología (Madrid) ; 38(5): 466-475, sept.-oct. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-177632

RESUMO

La vía de Notch regula procesos importantes en el riñón implicados en el desarrollo embrionario y en situaciones de agresión tisular. Así, en una gran variedad de nefropatías crónicas humanas se ha descrito una activación local de este sistema, sugiriendo que algunos de sus componentes podrían ser biomarcadores de daño renal. Los estudios realizados en modelos experimentales, modulando genéticamente componentes de la vía Notch o mediante su bloqueo farmacológico con inhibidores de la γ-secretasa, han demostrado la participación de esta vía en la regeneración renal, en la apoptosis de podocitos, en la proliferación y activación de fibroblastos y en la transición epitelio-mesenquimal de las células tubuloepiteliales. Estudios recientes sugieren una interacción entre las vías Notch y NF-κB, la cual podría jugar un papel relevante en el proceso inflamatorio renal. Por otra parte, en los últimos años se han descrito miRNA que son capaces de regular componentes de la vía Notch y modular sus respuestas. Todos estos datos indican que el bloqueo de la vía de señalización Notch podría representar una nueva opción terapéutica para la enfermedad renal


Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases


Assuntos
Humanos , Receptores Notch/metabolismo , Insuficiência Renal Crônica/terapia , Receptores Notch/antagonistas & inibidores , Transdução de Sinais , Fatores de Diferenciação de Crescimento/metabolismo , Angiotensina II/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo
6.
Rev. esp. patol. torac ; 30(2): 130-135, jun. 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-180249

RESUMO

En el tejido pulmonar de modelos murinos, la angiotensina II induce la proliferación de fibroblastos, su diferenciación a miofibroblastos y la producción de procolágeno tras su unión al receptor I de la angiotensina. Hemos estudiado el comportamiento de fibroblastos pulmonares humanos procedentes de una línea celular comercial tras la estimulación con TGF-β1. Hemos observado que estos fibroblastos, cuando son estimulados, aumentan la expresión de bFGF, colágeno y α-SMA. Tras el bloqueo del receptor de Angiotensina II con Losartan a una concentración de 10 µM y la estimulación con TGF- β1, se produce una disminución, tanto de los niveles de bFGF como de la concentración de colágeno, sin que llegue a alcanzar la significación estadística con respecto a las células no tratadas. En cuanto a la expresión de α-SMA como marcador de transformación a miofibroblastos, no había diferencias entre las células tratadas con TGF-β1 y TGF-β1 más losartán


In murine model lung tissue, angiotensin II induces the proliferation of fibroblasts, their distinction from myofibroblasts and procollagen production after its binding with the type 1 receptor. We have studied the behavior of human lung fibroblasts from a commercial cell line after stimulation with TGF-β1. We observed that those fibroblasts, when stimulated, increased bFGF, collagen and α-SMA expression. After blocking the angiotensin II receptor with losartan at a concentration of 10 µM and stimulation with TGF- β1, there was a decrease in both bFGF levels and collagen concentration, without reaching statistical significance with regard to untreated cells. With regard to α-SMA expression as an indicator of transformation to myofibroblasts, there were no differences between cells treated with TGF-β1 and TGF-β1 with losartan


Assuntos
Humanos , Fibroblastos/citologia , Fibrose Pulmonar Idiopática/fisiopatologia , Angiotensina II , Modelos Animais , Fator de Crescimento Transformador beta
8.
An. sist. sanit. Navar ; 40(2): 291-294, mayo-ago. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-165878

RESUMO

El olmesartán es un antagonista del receptor tipo 1 de la angiotensina II utilizado habitualmente en el tratamiento de pacientes con hipertensión arterial. Recientemente se han descrito varios casos de enteropatía sprue-like asociados al uso de este fármaco, con afectación clínica importante y total remisión tras la retirada del mismo. Se presenta el caso de un varón de 64 años, con antecedentes de hipertensión arterial en tratamiento con olmesartan-amlodipino con clínica de diarrea y pérdida de peso severas, atrofia vellositaria en biopsia duodenal sin criterios de enfermedad celiaca y remisión completa del cuadro tras la supresión del olmesartán. Basado en los hallazgos del caso clínico presentado, se revisan las manifestaciones clínicas e histopatológicas así como el curso evolutivo de una posible causa de enteropatía farmacológica recientemente descrita (AU)


Olmesartan is an angiotensin II type 1 receptor blocker commonly used in the treatment of hypertension. Several cases of sprue-like enteropathy associated with the use of this drug have been described which, even with important signs and limitations for the patient, present a full recovery after discontinuing the use of olmesartan. The case of a 64 year-old patient is presented, diagnosed with hypertension, under treatment with olmesartan- amlodipine, with chronic diarrhoea and villous atrophy on intestinal biopsies without diagnostic criteria for celiac disease and with complete remission after suspending discontinuing the use of olmesartan. Based on the clinical features presented by the case reported, the clinical and anatomopathological findings are described as well as the evolution of drug-induced enteropathy (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Combinação Besilato de Anlodipino e Olmesartana Medoxomila/efeitos adversos , Síndromes de Malabsorção/induzido quimicamente , Síndromes de Malabsorção/complicações , Angiotensina II/efeitos adversos , Gastroscopia/métodos , Atrofia/induzido quimicamente , Imuno-Histoquímica , Diagnóstico Diferencial , Diarreia/complicações , Diarreia/diagnóstico
9.
J. physiol. biochem ; 72(3): 381-392, sept. 2016. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-168282

RESUMO

The prostate gland is a part of the male reproductive tract which produces both angiotensin II (Ang II) and relaxin 2 (RLN2). The present study analyzes the effect of both these peptide hormones at concentration 10−8M on viability, proliferation, adhesion, migration, and invasion of normal prostate epithelial cells (PNT1A). Improved survival in two- and three-dimensional cell cultures was noted as well as visual changes in colony size and structure in Geltrex™. Stimulatory influence on cell viability of each peptide applied single was lower than in combination. Enhanced survival of PNT1A cells appears to be associated with increased BCL2/BAX messenger RNA (mRNA) expression ratio. Modulation of cell spreading and cell-extracellular matrix adhesion dynamics were also altered as an influence of tested hormone application. However, long-term Ang II and RLN2 effects may lead to an increase of normal prostate cell migration and invasion abilities. Moreover, gelatin zymography revealed that both gelatinases A and B were augmented by Ang II treatment, whereas RLN2 significantly stimulated only MMP-9 secretion. These results support the hypothesis that deregulation of locally secreted peptide hormones such as Ang II and RLN2 may take part in the development of certain cancers, including prostate cancer. Moreover, the observed ability of relaxin 2 to act as a regulator of mRNA expression levels not only LGR7 but also classic angiotensin receptors suggested that renin-angiotensin system and relaxin family peptide system are functionally linked (AU)


No disponible


Assuntos
Humanos , Masculino , Apoptose , Angiotensina II/metabolismo , Regulação da Expressão Gênica , Mucosa/metabolismo , Próstata/metabolismo , Relaxina/metabolismo , Membrana Basal/fisiologia , Fenômenos Fisiológicos Celulares , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores Acoplados a Proteínas G , Proteína X Associada a bcl-2 , RNA Mensageiro/metabolismo , Receptores de Peptídeos
10.
J. physiol. biochem ; 72(1): 1-8, mar. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-168202

RESUMO

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3 mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3 μg/kg/min) and/or Ang II (10 ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36 % (P < 0.05) when L-NAME and meclofenamate were infused simultaneously. PBF was similarly reduced by L-NAME (12 %), meclofenamate (17 %) or L-NAME + meclofenamate (19 %). Ang II did not modify OMBF, but it led to a similar decrease (P < 0.05) in OMBF when it was administered to rats with reduced NO (32 %), PGs (36 %) or NO and PGs (37 %) synthesis. In contrast, the fall in PBF induced by Ang II (12 %) was enhanced (P < 0.05) by the simultaneous PGs (30 %) or PGs and NO (31 %) synthesis inhibition but not in L-NAME-treated rats (20 %). This study presents novel findings suggesting that blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced (AU)


Assuntos
Animais , Masculino , Ratos , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Angiotensina II/fisiologia , Medula Renal/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Ratos Wistar , Taxa de Filtração Glomerular
12.
Rev. clín. esp. (Ed. impr.) ; 215(7): 363-370, oct. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-141809

RESUMO

Antecedentes y objetivos. Analizar las características clínicas diferenciales en función del sexo en pacientes con insuficiencia cardiaca (IC) en cuanto a etiología, comorbilidad, desencadenantes, tratamiento, estancia hospitalaria y mortalidad global al año. Pacientes y método. Se utilizaron los datos del registro RICA, cohorte prospectiva multicéntrica de pacientes hospitalizados en servicios de Medicina Interna por IC con seguimiento de un año. Se analizaron las diferencias de género en cuanto a la etiología de la cardiopatía, comorbilidad, factor desencadenante, fracción de eyección de ventrículo izquierdo, situación funcional, estado mental, tratamiento, estancia y mortalidad al año. Resultados. Se incluyeron 1772 pacientes (47,2% varones). Las mujeres eran mayores que los varones (p<0,001), tenían mayor prevalencia de hipertensión, obesidad, enfermedad renal crónica, fibrilación auricular y fracción de eyección de ventrículo izquierdo preservada (p<0,001). Entre los varones predominaban los antecedentes de infarto de miocardio, enfermedad pulmonar obstructiva crónica, arteriopatía periférica (p<0,001) y anemia (p=0,02). En las mujeres predominó la etiología hipertensiva, seguida de la valvular. Los principales desencadenantes fueron la hipertensión y fibrilación auricular. El tratamiento con beta-bloqueantes, IECA y/o ARA II no difirió en función del sexo. Las mujeres tenían peor capacidad funcional (p<0,001) según el índice de Barthel. Tras ajustar por edad y otros factores pronósticos, la mortalidad al año fue menor entre las mujeres RR:0,69 (IC 95% 0,53-0,89; p=0,004). Conclusiones. La IC en la mujer se presenta a edad más avanzada y con diferente comorbilidad. Predomina la etiología hipertensiva y valvular, con fracción de eyección de ventrículo izquierdo preservada, y la mortalidad ajustada por la edad es menor que en el varón (AU)


History and objectives: To analyze the differential clinical characteristics according to gender of patients with heart failure in terms of etiology, comorbidity, triggers, treatment, hospital stay and overall mortality at one year. Patients and method: We employed data from the RICA registry, a multicenter prospective cohort of patients hospitalized in internal medicine departments for heart failure, with a follow up of one year. We analyzed the differences between the gender in terms of the etiology of the heart disease, comorbidity, triggers, left ventricle ejection fraction, functional state, mental condition, treatment, length of stay and mortality at 1 year. Results: A total of 1772 patients (47.2% men) were included. The women were older than the men (p<.001) and had a higher prevalence of hypertension, obesity, chronic kidney disease, atrial fibrillation and preserved left ventricle ejection fraction (p<.001). The men’s medical history had a predominance of myocardial infarction, chronic obstructive pulmonary disease, peripheral arteriopathy (p<.001) and anemia (p=.02). In the women, a hypertensive etiology was predominant, followed by valvular. The main triggers were hypertension and atrial fibrillation. Treatment with beta-blockers, ACEIs and/or ARBs did not differ by sex. The women had poorer functional capacity (p<.001), according to the Barthel index. After adjusting for age and other prognostic factors, the mortality at one year was lower among the women (RR: 0.69; 95% CI 0.53-0.89; p=.004). Conclusions: HF in women occurs at a later age and with different comorbidities. The hypertensive and valvular etiology is predominant, with preserved left ventricle ejection fraction, and the age-adjusted mortality is lower than in men (AU)


Assuntos
Feminino , Humanos , Masculino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Prognóstico , Tempo de Internação/economia , Tempo de Internação/tendências , Fibrilação Atrial/epidemiologia , Identidade de Gênero , Comorbidade , Estudos de Coortes , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/prevenção & controle , Frequência Cardíaca/fisiologia , Angiotensina II/uso terapêutico , Análise Multivariada
14.
Rev. esp. cardiol. (Ed. impr.) ; 68(7): 562-570, jul. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-138856

RESUMO

Introducción y objetivos. La activación tanto del sistema nervioso simpático como del sistema renina-angiotensina-aldosterona está estrechamente relacionada con la hipertensión arterial pulmonar. Nuestra hipótesis era que la simpatectomía renal reduce la actividad del sistema renina-angiotensina-aldosterona e inhibe la progresión de la hipertensión arterial pulmonar. Métodos. Se asignó aleatoriamente a un total de 22 perros beagle a tres grupos de estudio. Se efectuaron determinaciones de la dinámica pulmonar de esos animales antes y 8 semanas después de la inyección de 0,1 ml/kg de dimetilformamida (perros de control) o de 2 mg/kg de deshidromonocrotalina (perros con hipertensión arterial pulmonar y perros con hipertensión arterial pulmonar + simpatectomía renal). Ocho semanas después de la inyección, se determinaron las concentraciones de neurohormonas y se evaluó la morfología del tejido pulmonar. Resultados. Se observó un aumento significativo de la concentración de angiotensina II y endotelina-1 en plasma después de 8 semanas en los perros con hipertensión arterial pulmonar, y los valores obtenidos en los tejidos pulmonares de estos animales eran superiores a los de los perros del grupo de control y el grupo de simpatectomía renal (medias: angiotensina II, 65 ± 9,8 frente a 38 ± 6,7 y 46 ± 8,1; endotelina-1, 96 ± 10,3 frente a 54 ± 6,2 y 67 ± 9,4; p < 0,01). La deshidromonocrotalina aumentó la presión arterial pulmonar media (16 ± 3,4 frente a 33 ± 7,3 mmHg; p < 0,01), y la simpatectomía renal evitó que se produjera este aumento. La proliferación celular del músculo liso pulmonar fue mayor en los perros con hipertensión arterial pulmonar que en los animales de los grupos de control y de hipertensión arterial pulmonar + simpatectomía renal. Conclusiones. La simpatectomía renal atenúa el remodelado vascular pulmonar y reduce la presión arterial pulmonar en la hipertensión arterial pulmonar experimental. El efecto de la simpatectomía renal puede contribuir a reducir las concentraciones de neurohormonas (AU)


Introduction and objectives. Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Methods. Twenty-two beagles were randomized into 3 groups. The dogs’ pulmonary dynamics were measured before and 8 weeks after injection of 0.1 mL/kg dimethylformamide (control dogs) or 2 mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Results. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs (AU)


Assuntos
Animais , Cães , Feminino , Humanos , Masculino , Simpatectomia/métodos , Simpatectomia/veterinária , Hipertensão/tratamento farmacológico , Hipertensão/cirurgia , Hipertensão/veterinária , Sistema Renina-Angiotensina , Sistema Renina-Angiotensina/fisiologia , Modelos Animais , Ketamina/uso terapêutico , 35170/métodos , Sistema Nervoso Simpático , Angiotensina II/uso terapêutico , Endotelina-1/uso terapêutico , Pentobarbital/uso terapêutico , Dimetilformamida/uso terapêutico , Hemodinâmica
19.
J. physiol. biochem ; 70(2): 465-478, jun. 2014.
Artigo em Inglês | IBECS | ID: ibc-122967

RESUMO

The aim of this study was to assess whether endogenous Ang II and oxidative stress produced by acute hypertonic sodium overload may regulate the expression of aquaporin-1 (AQP-1) and aquaporin-2 (AQP-2) in the kidney. Groups of anesthetized male Sprague–Dawley rats were infused with isotonic saline solution (control) or with hypertonic saline solution (Na group, 1 M NaCl), either alone or with losartan (10 mg kg−1) or tempol (0.5 mg min−1 kg−1) during 2 h. Renal function parameters were measured. Groups of unanesthetized animals were injected intraperitoneally with hypertonic saline solution, with or without free access to water intake, Na+W, and Na−W, respectively. The expression of AQP-1, AQP-2, Ang II, eNOS, and NF-kB were evaluated in the kidney by Western blot and immunohistochemistry. AQP-2 distribution was assessed by immunofluorescence. Na group showed increased natriuresis and diuresis, and Ang II and NF-kB expression, but decreased eNOS expression. Losartan or tempol enhanced further the diuresis, and AQP-2 and eNOS expression, as well as decreased Ang II and NF-kB expression. Confocal immunofluorescence imaging revealed labeling of AQP-2 in the apical plasma membrane with less labeling in the intracellular vesicles than the apical membrane in kidney medullary collecting duct principal cells both in C and Na groups. Importantly, our data also show that losartan and tempol induces a predominantly accumulation of AQP-2 in intracellular vesicles. In unanesthetized rats, Na+W group presented increased diuresis, natriuresis, and AQP-2 expression (112 ± 25 vs 64 ± 16; *p < 0.05). Water deprivation increased plasma sodium and diuresis but decreased AQP-2 (46 ± 22 vs 112 ± 25; §p < 0.05) and eNOS expression in the kidney. This study is a novel demonstration that renal endogenous Ang II-oxidative stress, induced in vivo in hypernatremic rats by an acute sodium overload, regulates AQP-2 expression


Assuntos
Animais , Ratos , Hiponatremia/tratamento farmacológico , Estresse Oxidativo , Aquaporinas , Angiotensina II/farmacocinética , Substâncias Protetoras/farmacocinética , Modelos Animais de Doenças
20.
J. physiol. biochem ; 70(2): 509-523, jun. 2014.
Artigo em Inglês | IBECS | ID: ibc-122971

RESUMO

In the present study, we investigated the role of angiotensin type I (AT1) receptor in reactive oxygen species (ROS) generation and mitogen-activated protein kinases (MAPK) activation induced by acute ethanol intake in resistance arteries. We also evaluated the effect of ethanol on platelet-derived growth factor receptors (PDGF-R) phosphorylation and the role of this receptor on ROS generation by ethanol. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. Acute ethanol intake did not alter angiotensin I or angiotensin II levels in the rat mesenteric arterial bed (MAB). Ethanol induced vascular oxidative stress, and this response was not prevented by losartan (10 mg/kg; p.o. gavage), a selective AT1 receptor antagonist. MAB from ethanol-treated rats displayed increased SAPK/JNK and PDGF-R phosphorylation, responses that were not prevented by losartan. The phosphorylation levels of protein kinase B (Akt) and eNOS were not affected by acute ethanol intake. MAB nitrate levels and the reactivity of this tissue to acetylcholine, phenylephrine, and sodium nitroprusside were not affected by ethanol intake. Ethanol did not alter plasma antioxidant capacity, the levels of reduced glutathione, or the activities of superoxide dismutase and catalase in the rat MAB. Short-term effects of ethanol (50 mmol/l) were evaluated in vascular smooth muscle cells (VSMC) isolated from rat MAB. Ethanol increased ROS generation, and this response was not affected by AG1296, a PDGF-R inhibitor, or losartan. Finally, ethanol did not alter MAPK or PDGF-R phosphorylation in cultured VSMC. Our study provides novel evidence that acute ethanol intake induces ROS generation, PDGF-R phosphorylation, and MAPK activation through AT(1)-independent mechanisms in resistance arteries in vivo. MAPK and PDGF-R play a role in vascular signaling and cardiovascular diseases and may contribute to the vascular pathobiology of ethanol


Assuntos
Animais , Ratos , Etanol/farmacocinética , Consumo de Bebidas Alcoólicas/fisiopatologia , Quinases de Proteína Quinase Ativadas por Mitógeno , Resistência Vascular , Fosforilação , Arteriopatias Oclusivas/fisiopatologia , Espécies Reativas de Oxigênio , Angiotensina I , Angiotensina II , Modelos Animais de Doenças
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