45 results on '"rocher, Asunción"'
Search Results
2. Intermittent Hypoxia and Diet-Induced Obesity on the Intestinal Wall Morphology in a Murine Model of Sleep Apnea
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Valverde-Pérez, Esther, Olea, Elena, Obeso, Ana, Prieto-Lloret, Jesús, Rocher, Asunción, Gonzalez-Obeso, Elvira, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Conde, Sílvia V., editor, Iturriaga, Rodrigo, editor, del Rio, Rodrigo, editor, Gauda, Estelle, editor, and Monteiro, Emília C., editor
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- 2023
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3. Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea.
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Olea, Elena, Valverde-Pérez, Esther, Docio, Inmaculada, Prieto-Lloret, Jesus, Aaronson, Philip I., and Rocher, Asunción
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GUINEA pigs ,SLEEP apnea syndromes ,CAROTID body ,PULMONARY arterial hypertension ,CAROTID intima-media thickness ,ENDOTHELIUM ,PULMONARY artery - Abstract
Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima–media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO
2 , 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Chronic Intermittent Hypoxia-Induced Dysmetabolism Is Associated with Hepatic Oxidative Stress, Mitochondrial Dysfunction and Inflammation
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Fernandes, Joana L., primary, Martins, Fátima O., additional, Olea, Elena, additional, Prieto-Lloret, Jesus, additional, Braga, Patrícia C., additional, Sacramento, Joana F., additional, Sequeira, Catarina O., additional, Negrinho, Ana P., additional, Pereira, Sofia A., additional, Alves, Marco G., additional, Rocher, Asunción, additional, and Conde, Silvia V., additional
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- 2023
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5. Mitochondrial Complex I Dysfunction and Peripheral Chemoreflex Sensitivity in a FASTK-Deficient Mice Model
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Gomez-Niño, Angela, Docio, Inmaculada, Prieto-Lloret, Jesus, Simarro, Maria, de la Fuente, Miguel A., Rocher, Asuncion, COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, Rezaei, Nima, Series Editor, Gauda, Estelle B., editor, Monteiro, Maria Emilia, editor, Prabhakar, Nanduri, editor, Wyatt, Christopher, editor, and Schultz, Harold D., editor
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- 2018
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6. Adrenal Medulla Chemo Sensitivity Does Not Compensate the Lack of Hypoxia Driven Carotid Body Chemo Reflex in Guinea Pigs
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Olea, Elena, Gonzalez-Obeso, Elvira, Agapito, Teresa, Obeso, Ana, Rigual, Ricardo, Rocher, Asuncion, Gomez-Niño, Angela, COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, Rezaei, Nima, Series Editor, Gauda, Estelle B., editor, Monteiro, Maria Emilia, editor, Prabhakar, Nanduri, editor, Wyatt, Christopher, editor, and Schultz, Harold D., editor
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- 2018
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7. Analysis of Bone Histomorphometry in Rat and Guinea Pig Animal Models Subject to Hypoxia
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Usategui-Martín, Ricardo, primary, Del Real, Álvaro, additional, Sainz-Aja, José A., additional, Prieto-Lloret, Jesús, additional, Olea, Elena, additional, Rocher, Asunción, additional, Rigual, Ricardo J., additional, Riancho, José A., additional, and Pérez-Castrillón, José Luis, additional
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- 2022
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8. Some Reflections on Intermittent Hypoxia. Does it Constitute the Translational Niche for Carotid Body Chemoreceptor Researchers?
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Gonzalez, Constancio, Yubero, Sara, Gomez-Niño, M. Angela, Agapito, Teresa, Rocher, Asuncion, Rigual, Ricardo, Obeso, Ana, Montserrat, Jose M., Nurse, Colin A., editor, Gonzalez, Constancio, editor, Peers, Chris, editor, and Prabhakar, Nanduri, editor
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- 2012
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9. Serotonin Dynamics and Actions in the Rat Carotid Body: Preliminary Findings
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Ramirez, Maria, Gallego-Martin, Teresa, Olea, Elena, Rocher, Asuncion, Obeso, Ana, Gonzalez, Constancio, Nurse, Colin A., editor, Gonzalez, Constancio, editor, Peers, Chris, editor, and Prabhakar, Nanduri, editor
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- 2012
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10. Cyclic AMP and Epac Contribute to the Genesis of the Positive Interaction Between Hypoxia and Hypercapnia in the Carotid Body
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Ramirez, Maria, Almaraz, Laura, Gonzalez, Constancio, Rocher, Asuncion, Nurse, Colin A., editor, Gonzalez, Constancio, editor, Peers, Chris, editor, and Prabhakar, Nanduri, editor
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- 2012
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11. Intracellular Ca2+ Deposits and Catecholamine Secretion by Chemoreceptor Cells of the Rabbit Carotid Body
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Obeso, Ana, Rocher, Asunción, López-López, José Ramón, González, Constancio, Zapata, Patricio, editor, Eyzaguirre, Carlos, editor, and Torrance, Robert W., editor
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- 1996
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12. Hypoxia inhibits the synthesis of phosphoinositides in the rabbit carotid body
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Rigual, R., Cachero, M. Teresa G., Rocher, Asunción, and González, Constancio
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- 1999
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13. Peripheral Dopamine 2-Receptor Antagonist Reverses Hypertension in a Chronic Intermittent Hypoxia Rat Model
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Olea, Elena, primary, Docio, Inmaculada, additional, Quintero, Miguel, additional, Rocher, Asunción, additional, Obeso, Ana, additional, Rigual, Ricardo, additional, and Gomez-Niño, Angela, additional
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- 2020
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14. Role of voltage-dependent calcium channels in stimulus–secretion coupling in rabbit carotid body chemoreceptor cells
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Rocher, Asunción, Geijo-Barrientos, Emilio, Cáceres, Ana Isabel, Rigual, Ricardo, González, Constancio, and Almaraz, Laura
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- 2005
15. Isolation and partial characterization of a new ribosome-inactivating protein from Petrocoptis glaucifolia (Lag.) Boiss
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Arias, F. Javier, Rojo, M. Angeles, Ferreras, J. Miguel, Iglesias, Rosario, Muñoz, Raquel, Rocher, Asunción, Mendez, Enrique, Barbieri, Luigi, and Girbés, Tomás
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- 1992
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16. Intracellular Ca2+ Deposits and Catecholamine Secretion by Chemoreceptor Cells of the Rabbit Carotid Body
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Obeso, Ana, primary, Rocher, Asunción, additional, López-López, José Ramón, additional, and González, Constancio, additional
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- 1996
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17. Estrogens and age influence on pulmonary hypertension in female rats
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Olea, Elena, Rocher, Asunción, Docio, Inmaculada, Gómez-Niño, A., Obeso, Ana, and Prieto-Lloret, Jesús
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Trabajo presentado en la 2ª Reunión de investigación en hipertensión pulmonar, celebrado en Madrid (España) el 2 de febrero de 2018.
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- 2018
18. Gender influence on carotid body sensitization and pulmonary arterial hypertension in chronic hypoxic rats
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Olea, Elena, Prieto-Lloret, Jesús, Gordillo, Ana, Docio, Inmaculada, Obeso, Ana, Gómez-Niño, A., and Rocher, Asunción
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Trabajo presentado al XXXIX Congreso de la Sociedad Española de Ciencias Fisiológicas (SECF), celebrado en Cádiz del 18 al 21 de septiembre de 2018.
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- 2018
19. Physiopathological cardiorespiratory responses to two chronic hypoxic treatments in rats
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Gordillo Cano, Ana, Ayllón, Marta, Prieto-Lloret, Jesús, Docio, Inmaculada, Olea, Elena, Gómez-Niño, A., Obeso, Ana, and Rocher, Asunción
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Trabajo presentado a las 11as Jornadas de Formación del CIBERES (Jornadas conjuntas con CIBERONC), celebradas en el Instituto de Salud Carlos III (Madrid) del 15 al 16 de noviembre de 2018.
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- 2018
20. Pulmonary hypertension in female aats: estrogens and age influence
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Obeso, Ana, Olea, Elena, Rocher, Asunción, Gordillo, Ana, Gómez-Niño, A., and Prieto-Lloret, Jesús
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Resumen del trabajo presentado al European Respiratory Society (ERS) International Congress, celebrado en Paris (Francia) del 15 al 19 de septiembre de 2018., [Rationale & Aim]: In spite of the protective effect of estrogens on the systemic and pulmonary vasculature, female sex has been shown to be a risk factor for pulmonary arterial hypertension (PAH), namely, the estrogen paradox. Our aim was to study the PAH development in young female (CH3m) respect to old female (CH24m) rats exposed to chronic hypoxia (CH)., [Methods]: We exposed young and old female rats to normobaric hypoxic atmosphere (10%O2/PO2≈70 mmHg, 14 days). We measured pulmonary artery (PA) pressure by right heart catheterization, hematocrit, Fulton index, and endothelial function in PA using small vessels myography and compared to control females breathing air (C3m and C24m)., [Results]: PA pressure was lower in CH24m vs. CH3m (17.2±1.6mmHg, n=8 vs. 22.5±1.1mmHg, n=6; p, [Conclusion]: Hemodynamics and vasomotor effects of CH were ameliorated in CH24m compared to CH3m rats. Old animals showed PA endothelial damage and CH didn´t worse it. In CH3m no significant damage was observed. The decreased estrogen levels in old female rats could be the responsible for the observed results.
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- 2018
21. Sex and age differences in pulmonary vascular responses in a chronic hypoxic rat model
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Olea, Elena, primary, Prieto-Lloret, Jesús, additional, Gordillo, Ana, additional, Gomez-Niño, Angela, additional, Obeso, Ana, additional, Rigual, Ricardo, additional, and Rocher, Asunción, additional
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- 2019
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22. Significance of ROS in oxygen sensing in cell systems with sensitivity to physiological hypoxia
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Gonzalez, Constancio, Sanz-Alfayate, Gloria, Agapito, M.Teresa, Gomez-Niño, Angela, Rocher, Asunción, and Obeso, Ana
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- 2002
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23. Is the guinea pig a full negative model to study the carotid mediated chronic intermittent hipoxia effects?
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Docio, Inmaculada, Olea, Elena, Gallego-Martin, Teresa, Obeso, Ana, Rocher, Asunción, Gómez-Niño, A., Ministerio de Economía y Competitividad (España), Junta de Castilla y León, and Instituto de Salud Carlos III
- Abstract
Resumen del póster presentado al Joint Meeting of the American Physiological Society and the Physiological Society, celebrado en Dublin (Irlanda) del 29 al 31 de julio de 2016., Chronic Intermittent Hypoxia (CIH) is considered to be one of the main causes of systemic arterial hypertension observed in the obstructive sleep apnea syndrome. It is thought that repetitive episodes of hypoxia/re-oxygenation produce oxidative stress, inflammation and sympathetic hyperactivity, generating endothelial dysfunction and systemic hypertension. It has been proposed that the repeated carotid body (CB) stimulation produced by CIH would induce CB sensitization, increasing chemoreceptor input to the brainstem that originates an exaggerated sympathetic reflex with a rise of circulating catecholamine (CA) and hypertension. Unlike other rodents, preliminary data show a lack of CB sensitivity to acute hypoxia in guinea pigs, in which case, CIH would not induce CB sensitization and the effects derived from the CB hyperactivity would not be observed. Therefore, guinea pigs could be a negative control model to study the effects of CIH mediated by CB. In this study, experiments were performed on adult male Hartley guinea pigs (475±10 g; n=32) control or exposed to CIH (21% O2-80 s/5% O2-40s 8h/day; 30 days). Ventilatory parameters (tidal volume and respiratory rate) were measured in freely moving animals by whole body plethysmography; other measurements were performed on animals anaesthetized with a mixture of ketamine (100 mg/Kg) and diazepam (2 mg/Kg; ip.). Control and CIH guinea pig respiratory minute volume exhibited similar changes when acute hypoxic test was applied (399±5 vs 411±5 in air and 417±15 vs 456±17 ml/min/Kg in 10% O2; n=16). Values are means ± S.E.M. compared by ANOVA. There were no in vitro CB responses to acute hypoxia (CA secretion or Ca2+i changes) in either group of animals. No differences were found in mean arterial blood pressure (37±2 vs 43±3 mmHg; n=8), or in plasma and tissue CA levels (CB, adrenal medulla, renal artery) measured after exposure to CIH. The fact that the guinea pig CB is hypo-functional and is not sensitized by CIH would reinforce our working hypothesis: systemic effects associated to CIH in other species and absent in guinea pigs are due to the CB hyperactivity induced by CIH. However several unexpected results would indicate hypoxic activation of the sympathetic system during acute hypoxic test as increased arterial pulse pressure (20±1 mmHg in air and 28±2 mmHg in 10% O2; p, Supported by grants: MINECO BFU2015-70616R; ISCiii CIBER CB06/06/0050; JCyL BIO/VA11/15
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- 2016
24. Aging effects on carotid body and vascular responses from rats exposed to chronic intermittent hypoxia
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Olea, Elena, Docio, Inmaculada, Gallego-Martin, Teresa, Obeso, Ana, Agapito, Teresa, Gómez-Niño, A., Rocher, Asunción, Instituto de Salud Carlos III, and Ministerio de Economía y Competitividad (España)
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Aging ,Carotid body ,Catecholamines ,Intermittent hypoxia ,Ventilation - Abstract
Resumen del póster presentado al XXXVIII Congreso de la Sociedad Española de Ciencias Fisiológicas (SECF), celebrado en Zaragoza del 13 al 16 de septiembre de 2016., Chronic Intermittent Hypoxia (CIH) is considered one of the main causes of cardiovascular and metabolic alterations observed in the obstructive sleep apnea syndrome. Repetitive episodes of hypoxia/re-oxygenation produce oxidative stress and inflammation that could predispose to cumulative injury and acceleration of the aging process. Previous observations show that deleterious effects of CIH seem to be less pronounced in aged animals. It has also been reported that CIH produces sympathetic hyperactivity, endothelial dysfunction and systemic hypertension. Carotid body (CB) sensitization by recurrent hypoxic stimulation has been proposed as the origin of these alterations. The aim of this study is to compare vascular and CB responses and hypertensive changes in young and aged animals exposed to CIH, relating age and CIH induced effects. Four groups of male Wistar rats were used: young (3 months; n=32) and aged (18 months; n=32) in normoxia (C 3/18 months; n=16) and exposed to (21% O2-80 s/5% O2-40s 8h/day; 14 days) CIH (3/18 months; n=16). Ventilatory responsiveness to hypoxic and hypercapnic test was measured by whole body plethysmography. Aged rats ventilated less than younger under any conditions. On animals anaesthetized with ketamine (100 mg/Kg) and diazepam (5 mg/Kg; ip.), blood pO2, pCO2 and SatO2 were analyzed by gasometry at different inspired air O2 percentages (5-21%). In old control and CIH rats, SatO2 at PO2 ≤50 mmHg was lower than in young control rats. Mean arterial blood pressure (MABP) and pulse pressure were higher in aged than young control rats but got similar values after CIH. Vascular contractile responses were studied by wire myography. Using external carotid arteries, wall tension generated in response to phenylephrine (0.01 to 3μM) was higher in aged and CIH than young control rat arteries. Carbachol (10 μM) dependent relaxations were greater in young control than in aged and CIH rat arteries. Larger MABP and vascular properties alterations in aged animals could explain the lack of MABP increase observed in old rats after CIH. Conversely, CIH enhanced the CB secretory response to hypoxia (5% O2) in young and aged rats (250 vs. 300%), correlating with Cai 2+ increases in freshly dissociated chemoreceptor cells. Mechanisms underlying the enhanced CB reactivity to hypoxia induced by CIH could be due to a pro-oxidative status, as observed in other tissues., MINECO BFU2015-70616R; ISCiii CIBER CB06/06/0050.
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- 2016
25. From carotid body oxygen sensing to chronic intermittent hipoxia effects on spontaneous tumorigenesis. The journey of Constancio’s group
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Gallego-Martin, Teresa, Rocher, Asunción, Agapito, Teresa, Gómez-Niño, A., Rigual, Ricardo, Yubero, Sara, Gonzalez-Obeso, Elvira, Olea, Elena, Docio, Inmaculada, Obeso, Ana, Instituto de Salud Carlos III, European Commission, Asociación Española Contra el Cáncer, and Ministerio de Economía y Competitividad (España)
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Carotid body ,Intermittent hypoxia ,Tumorigenesis ,Oxygen sensing - Abstract
Resumen del trabajo presentado al XXXVIII Congreso de la Sociedad Española de Ciencias Fisiológicas (SECF), celebrado en Zaragoza del 13 al 16 de septiembre de 2016., The carotid body (CB) is a singular organ which senses variations of the arterial blood PO2, PCO2 and [H+]. In the middle of 1980s, based on our experimental data, our laboratory proposed the membrane hypothesis of acute hypoxic chemoreception formulating that the chemoreceptor cells decrease in arterial PO2 is detected by an oxygen sensor, and the reduction in the opening probability of O2-sensitive K+ channels (Lopez-Barneo et al., 1988) depolarizes chemoreceptor cells. Activation of voltage dependent Na+ and Ca2+ channels increases intracellular free [Ca2+] promoting release of catecholamines and other neurotransmitters, which augment the activity of the carotid sinus nerve producing hyperventilation (Gonzalez et al., 1994). Second messengers, such as cAMP, EPAC, and hydrogen sulphide, are capable to modulate the flow of information in the chemoreception transduction cascade (Rocher et al., 2009; Gallego-Martin et al., 2015). Nowadays, oxygen sensor identity remains unknown. Physiological systemic effects of CB activation have long been studied. In recent years, CB involvement in several pathological processes turns into a field of high interest. Some of these pathological processes are respiratory diseases that involve hypoxic situations, such as chronic sustained hypoxia in chronic obstructive pulmonary disease and chronic intermittent hypoxia (CIH) in obstructive sleep apnea (OSA). As a consequence of CIH, repetitive CB activation produces sympathetic overstimulation and redox imbalance, with high levels of reactive oxygen species (Agapito et al., 2009). CB overexcitation in OSA patients could be related to the appearance of cardiovascular pathologies (endotelial dysfunctions, hypertension, cardio- and cerebrovascular accidents), hepatometabolic alterations (obesity, insulin resistance, non-alcoholic hepatic steatosis), and neuropsychiatric diseases (anxiety, depression, dementia). Recently, it has been proposed a relationship between CIH, the main constitutive element of OSA, and cancer. Limited studies have evidenced that CIH augments growth and metastasis rate of implanted tumors in mice (Almendros et al 2013). In OSA patients, although with some discrepancies, an association between OSA and cancer incidence/mortality has been reported (Nieto et al., 2012). Discrepancies could be due to the large number of OSA-linked co-morbidities. Trying to simplify this complex pathological human situation, CIH as a single variable has been used to evaluate its effects on spontaneous tumorigenesis. In an old outbreed murine model, two intensities of CIH were applied (12% O2, moderate, and 7.5% O2, severe) mimicking two stages of OSA patients pathological situation. We have observed that long term (3 months) severe CIH augments spontaneous lung tumor incidence. These tumors are lung typical carcinoids, a type of neuroendocrine tumor. These findings could help to interpret cancer incidence in OSA patients and, on the other hand, they alert about the necessity of further designed human studies to evaluate if OSA could augment only specific types of cancer incidence., BFU2015-70616-R, MINECO/FEDER, UE; CIBERCB06/06/0050, CIBERES; APRO-I Valladolid, Asociación Española Contra el Cáncer.
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- 2016
26. Aged mice obstructive sleep apnoea model with spontaneous tumorigenesis: physiological parameters
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Gallego-Martin, Teresa, primary, Gordillo, Ana, additional, Gonzalez-Obeso, Elvira, additional, Olea, Elena, additional, Docio, Inmaculada, additional, Almendros, Isaac, additional, Obeso, Ana, additional, and Rocher, Asunción, additional
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- 2017
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27. Hypoxic pulmonary vasoconstriction, carotid body function and erythropoietin production in adult rats perinatally exposed to hyperoxia
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Prieto-Lloret, Jesús, Ramirez, Maria, Olea, Elena, Castañeda, J., Yubero, Sara, Agapito, Teresa, Gómez-Niño, A., Rocher, Asunción, Rigual, Ricardo, Obeso, Ana, Pérez-Vizcaino, Francisco, González, Constancio, Ministerio de Economía y Competitividad (España), and Instituto de Salud Carlos III
- Abstract
Adult mammalians possess three cell systems that are activated by acute bodily hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (CBCC) and erythropoietin (EPO)-producing cells. In rats, chronic perinatal hyperoxia causes permanent carotid body (CB) atrophy and functional alterations of surviving CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal hyperoxia (55–60% O2 for the last 5–6 days of pregnancy and 4 weeks after birth). Perinatal hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by antioxidant supplementation in the diet. O2-sensitivity of K+ currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal hyperoxia also abrogated responses elicited by hypoxia on catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal hyperoxia, comparable to oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional pneumonias, atelectases or general anaesthesia in adult life., This work was supported by Grants BFU2012-37459 from the Ministry of Economy and Competitiveness (Spain) and Grant CIBER CB06/06/0050 from the Institute of Health Carlos III (Spain) to C. G. Also supported by Grants SAF2011-28150 to F.P-V and SAF2010-22066-C02-02 to AC from the Ministry of Economy and Competitiveness (Spain).
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- 2015
28. Role of calcium channel remodeling in the reversal phenotypic switch of human coronary artery smooth muscle cells, and the effects of NSAIDs
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Muñoz, Eva, Sobradillo, Diego, Hernández-Morales, Miriam, Rocher, Asunción, Núñez, Lucía, Villalobos, Carlos, Junta de Castilla y León, Dirección General de Investigación Científica y Técnica, DGICT (España), and Consejo Superior de Investigaciones Científicas (España)
- Abstract
Resumen del trabajo presentado al Joint FEPS & XXXVI Spanish Physiological Society Congress (Sociedad Española de Ciencias Fisiológicas) celebrado en Santiago de Compostela (España) del 8 al 11 de septiembre de 2012., [Objectives]: Abnormal proliferation of vascular smooth muscle cells, a process related to ion channel remodeling, contribute to occlusive disorders including restenosis and atherosclerosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent VSMC proliferation and occlusive disorders by an unknown mechanism. We aimed at characterizing the role of calcium channel remodeling in the reversal phenotypic switch of cultured human coronary artery smooth muscle cells (hCASMCs) and the antiproliferative mechanism of NSAIDs. [Materials]: For this end we used cytosolic and mitochondrial calcium imaging and electrophysiological recordings in addition to real-time PCR and western blotting. [Results]: We found that early passage hCASMCs showed a proliferating phenotype, proliferation depending fully on store-operated calcium entry (SOCE), but not on voltage-operated calcium entry (VOCE). Proliferating hCASMCs showed large SOCE, SOCE-induced mitochondrial calcium uptake and Stim1 whereas VOCE was residual. NSAIDs inhibited SOCE as well as proliferation and migration. After a few passages hCASM cells switched to a non proliferating phenotype characterized by decreased SOCE and Stim1 and increased VOCE, Cav1.2 and VOCE-induced mitochondrial calcium uptake. NSAIDs failed to inhibit SOCE in the non-proliferating cells. [Conclusions]: We conclude that proliferating hCASMCs undergo a reversal phenotypic switch in culture towards quiescent cells mediated by remodeling of calcium channels that may reflect the changes underlying vascular occlusive disorders. NSAIDs inhibit SOCE and hCASMC proliferation and migration in a mitochondria-dependent, phenotypic specific manner., This work was funded by DIGICYT (BFU2009-08967) and Junta de Castilla y León, Spain (VA270A11-2). EM and DS were supported by predoctoral fellowships from FPI (DIGICYT) and JAE (CSI) programs, respectively.
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- 2012
29. Carotid body related functions in rats subjected to intermittent hypoxia, fed with high fat diet and both treatments applied simultaneously
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Yubero, Sara, Gallego-Martin, Teresa, Rocher, Asunción, Olea, Elena, González, Constancio, Obeso, Ana, Junta de Castilla y León, Ministerio de Economía y Competitividad (España), and Instituto de Salud Carlos III
- Abstract
Resumen del póster presentado al Joint FEPS & XXXVI Spanish Physiological Society Congress (Sociedad Española de Ciencias Fisiológicas) celebrado en Santiago de Compostela (España) del 8 al 11 de septiembre de 2012., [Objectives]: Obstructive sleep apnea creates an intermittent hypoxia (IH) every night during sleep time. Repetitive stimulation by IH sensitizes the carotid body (CB) causing permanent reflex sympathetic activation which generates hypertension and a tendency to increase acute vascular accidents. Thus, the CB is at the origin of the cardiovascular pathology in the obstructive sleep apnea syndrome (OSAS). In addition, obesity is a known factor to generate or aggravate OSAS pathologies. [Materials]: We have studied the existence of interactions between IH and obesity to alter CB function to define if CB altered by IH and/or obesity modifies sympathetic related parameters. We used male Wistar rats fed for 12 weeks (3-6 months of age) with regular or high fat diet (HFD; 10 and 60% fat). We defined four groups: control (C), CIH, obese (O) and OIH. Protocol of IH was: 5% O2, 40s/ 21% O2, 80s, 8h/day, 15 days (weeks 10-12 of HFD or equivalent age in regular diet animals). [Results]: A. Parameters CB related. Dopamine (DA) and norepinephrine (NE) levels increased in the CB in CIH, O and OIH rats. In CIH and O rats DA and NE synthesis rates augmented, with a further increase in OIH rats. DA release induced by hypoxia augmented in CIH and that induced by high K+ augmented in CIH, O and OIH groups. Hypoxia and high CO2 elicited increases in minute ventilation (MV) was normal in O but diminished in CIH and OIH groups. B. Sympathetic related parameters. Plasma NE and epinephrine (E) levels were augmented in CIH, O, and OIH. Similarly NE levels increased in the renal artery of CIH, O, and OIH rats, and more importantly, NE rate of synthesis (a measure of NE release or sympathetic tone) augmented in CIH and more than doubled in O and OIH groups. Finally, mean arterial pressure (88 mmHg in C) was progressively higher IH, O and OIH rats. Findings were always expressed vs. C group. [Conclusions]: Thus, IH and obesity interact to modify CB function and sympathetic tone., BFU2007-61848, PT2009-0172, JCyL2011 (Sanidad) and CIBERES.
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- 2012
30. Serotonin dynamics in the rat carotid body
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Olea, Elena, Rocher, Asunción, González, Constancio, and Obeso, Ana
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Trabajo presentado como comunicación oral al XVIII International Meeting of the Society for Arterial Chemoreception celebrado en Ontario (Canadá) del 10 al 15 de julio del 2011., Supported by grants BFU2007-61848 (DGICYT) and CIBER CB06/06/0050 (ISCIII).
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- 2011
31. Effects of intermittent hypoxia on chemoreception
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González, Constancio, Agapito, Teresa, Rocher, Asunción, Gómez-Niño, A., Rigual, Ricardo, Yubero, Sara, and Obeso, Ana
- Abstract
Trabajo presentado como comunicación oral al XVIII International Meeting of the Society for Arterial Chemoreception celebrado en Ontario (Canadá) del 10 al 15 de julio del 2011., Supported by grants BFU2007-61848 (DGICYT) and CIBER CB06/06/0050 (ISCIII).
- Published
- 2011
32. EPAC signalling pathways are involved in low PO2 chemoreception in carotid body chemoreceptor cells
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Rocher, Asunción, Cáceres, Ana Isabel, Almaraz, Laura, González, Constancio, Dirección General de Investigación Científica y Técnica, DGICT (España), Instituto de Salud Carlos III, and Junta de Castilla y León
- Abstract
Chemoreceptor cells of the carotid bodies (CB) are activated by hypoxia and acidosis, responding with an increase in their rate of neurotransmitter release, which in turn increases the electrical activity in the carotid sinus nerve and evokes a homeostatic hyperventilation. Studies in isolated chemoreceptor cells have shown that moderate hypoxias (PO2 ≈ 46 mmHg) produces smaller depolarisations and comparable Ca2+ transients but a much higher catecholamine (CA) release response in intact CBs than intense acidic/hypercapnic stimuli (20% CO2, pH 6.6). Similarly, intense hypoxia (PO2 ≈ 20 mmHg) produces smaller depolarizations and Ca2+ transients in isolated chemoreceptor cells but a higher CA release response in intact CBs than a pure depolarizing stimulus (30-35 mM external K+). Studying the mechanisms responsible for these differences we have found the following. (1) Acidic hypercapnia inhibited ICa (∼60%; whole cell) and CA release (∼45%; intact CB) elicited by ionomycin and high K+. (2) Adenylate cyclase inhibition (SQ-22536; 80 μM) inhibited the hypoxic release response (>50%) and did not affect acidic/hypercapnic release, evidencing that the high gain of hypoxia to elicit neurotransmitter release is cAMP dependent. (3) The last effect was independent of PKA activation, as three kinase inhibitors (H-89, KT 5720 and Rp-cAMP; ≥ 10 × IC50) did not alter the hypoxic release response. (4) The Epac (exchange protein activated by cAMP) activator (8-pCPT-2′-O-Me-cAMP, 100 μM) reversed the effects of the cyclase inhibitor. (5) The Epac inhibitor brefeldin A (100 μM) inhibited (54%) hypoxic induced release. Our findings show for the first time that an Epac-mediated pathway mediates O2 sensing/transduction in chemoreceptor cells. © 2009 The Authors. Journal compilation © 2009 The Physiological Society., The work was supported by grants BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (FISS-ICIII), GR242, VA104A08 and SAN673-VA12/08 (JCyL) and IP052561 (ISCiii).
- Published
- 2009
33. Intracellular Ca2+ remodeling during the phenotypic journey of human coronary smooth muscle cells
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Muñoz, Eva, primary, Hernández-Morales, Miriam, additional, Sobradillo, Diego, additional, Rocher, Asunción, additional, Núñez, Lucía, additional, and Villalobos, Carlos, additional
- Published
- 2013
- Full Text
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34. Role of the amino-terminal domain of bacteriophage ø29 connector in DNA binding and packaging
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Donate, L. E., Valpuesta, José M., Rocher, Asunción, Méndez Cormán, Enrique, Rojo, Fernando, Salas, Margarita, Carrascosa, José L., Comisión Interministerial de Ciencia y Tecnología, CICYT (España), and Fundación Ramón Areces
- Abstract
The connector of bacteriophage phi 29 is required for prohead assembly, binds DNA, and drives DNA packaging into viral proheads. Limited proteolysis of the connector protein with endoproteinase Glu-C from Staphylococcus aureus V8 and chymotrypsin showed that a domain of the NH2-terminal region is involved in DNA binding and in the subsequent packaging into preformed proheads, but not in prohead assembly. Mutants in specific amino acids of the NH2-terminal domain, obtained by directed mutagenesis techniques, showed that the Ala1-Arg2-Lys3-Arg4 region of the connector is absolutely necessary for DNA packaging into the proheads as well as for efficient DNA binding., This work was partially supported by Grants PB87-0365 (to J. L. C.) and PB87-0323 (to M. S.) from the Comisi6n Interministerial de Ciencia y Tecnologia and by the Fundacibn Ram6n Areces. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "aduer- tisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Published
- 1992
35. Fernando de Castro and the discovery of the arterial chemoreceptors.
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Gonzalez, Constancio, Conde, Silvia V., Gallego-Martín, Teresa, Olea, Elena, Gonzalez-Obeso, Elvira, Ramirez, Maria, Yubero, Sara, Agapito, Maria T., Gomez-Niño, Angela, Obeso, Ana, Rigual, Ricardo, and Rocher, Asunción
- Subjects
CAROTID body ,SENSORY ganglia ,GLOSSOPHARYNGEAL nerve ,EPITHELIAL cells ,CHEMORECEPTORS - Abstract
When de Castro entered the carotid body (CB) field, the organ was considered to be a small autonomic ganglion, a gland, a glomus or glomerulus, or a paraganglion. In his 1928 paper, de Castro concluded: "In sum, the Glomus caroticum is innervated by centripetal fibers, whose trophic centers are located in the sensory ganglia of the glossopharyngeal, and not by centrifugal [efferent] or secretomotor fibers as is the case for glands; these are precisely the facts which lead to suppose that the Glomus caroticum is a sensory organ." A few pages down, de Castro wrote: "The Glomus represents an organ with multiple receptors furnished with specialized receptor cells like those of other sensory organs [taste buds?]. . .As a plausible hypothesis we propose that the Glomus caroticum represents a sensory organ, at present the only one in its kind, dedicated to capture certain qualitative variations in the composition of blood, a function that, possibly by a reflex mechanism would have an effect on the functional activity of other organs. . . Therefore, the sensory fiber would not be directly stimulated by blood, but via the intermediation of the epithelial cells of the organ, which, as their structure suggests, possess a secretory function which would participate in the stimulation of the centripetal fibers." In our article we will recreate the experiments that allowed Fernando de Castro to reach this first conclusion. Also, we will scrutinize the natural endowments and the scientific knowledge that drove de Castro to make the triple hypotheses: the CB as chemoreceptor (variations in blood composition), as a secondary sensory receptor which functioning involves a chemical synapse, and as a center, origin of systemic reflexes. After a brief account of the systemic reflex effects resulting from the CB stimulation, we will complete our article with a general view of the cellular-molecular mechanisms currently thought to be involved in the functioning of this arterial chemoreceptor. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
36. Intracellular Ca2+ remodeling during the phenotypic journey of human coronary smooth muscle cells.
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Muñoz, Eva, Hernández-Morales, Miriam, Sobradillo, Diego, Rocher, Asunción, Núñez, Lucía, and Villalobos, Carlos
- Abstract
Abstract: Vascular smooth muscle cells undergo phenotypic switches after damage which may contribute to proliferative disorders of the vessel wall. This process has been related to remodeling of Ca
2+ channels. We have tested the ability of cultured human coronary artery smooth muscle cells (hCASMCs) to return from a proliferative to a quiescent behavior and the contribution of intracellular Ca2+ remodeling to the process. We found that cultured, early passage hCASMCs showed a high proliferation rate, sustained increases in cytosolic [Ca2+ ] in response to angiotensin II, residual voltage-operated Ca2+ entry, increased Stim1 and enhanced store-operated currents. Non-steroidal anti-inflammatory drugs inhibited store-operated Ca2+ entry and abolished cell proliferation in a mitochondria-dependent manner. After a few passages, hCASMCs turned to a quiescent phenotype characterized by lack of proliferation, oscillatory Ca2+ response to angiotensin II, increased Ca2+ store content, enhanced voltage-operated Ca2+ entry and Cav 1.2 expression, and decreases in Stim1, store-operated current and store-operated Ca2+ entry. We conclude that proliferating hCASMCs return to quiescence and this switch is associated to a remodeling of Ca2+ channels and their control by subcellular organelles, thus providing a window of opportunity for targeting phenotype-specific Ca2+ channels involved in proliferation. [Copyright &y& Elsevier]- Published
- 2013
- Full Text
- View/download PDF
37. Cellular mechanisms of oxygen chemoreception in the carotid body
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González, Constancio, primary, López-López, JoséRamón, additional, Obeso, Ana, additional, Pérez-García, María Teresa, additional, and Rocher, Asunción, additional
- Published
- 1995
- Full Text
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38. Characterization of distinct α- and γ-type gliadins and low molecular weight components from wheat endosperm as coeliac immunoreactive proteins
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Rocher, Asunción, primary, Soriano, Fernando, additional, Molina, Enrique, additional, González-Limas, Gabriel, additional, and Méndez, Enrique, additional
- Published
- 1995
- Full Text
- View/download PDF
39. Primary structure of ω-hordothionin, a member of a novel family of thionins from barley endosperm, and its inhibition of protein synthesis in eukaryotic and prokaryotic cell-free systems.
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Méndez, Enrique, rocher, Asunción, Calero, Miguel, Girbés, Tomáo, Citores, Lucís, and Soriano, Fernando
- Subjects
- *
AMINO acids , *ORGANIC acids , *LIQUID chromatography , *CHROMATOGRAPHIC analysis , *GEL electrophoresis , *ELECTROPHORESIS - Abstract
A new sulfur-rich basic polypeptide. so called ω-hordothionin, has been isolated from barley endosperm by extractions with NaCl and ammonium bicarbonate followed by reverse-phase high performance liquid chromatography. Purified ω-hordothionin was found to be homogeneous by SDS/polyacrylamide gel electrophoresis, N-terminal amino-acid sequencing and electrospray-ionization mass spectrometric analysis. The complete primary structure of ω-hordothionin was determined by automatic degradation of the intact molecule and peptides obtained by proteotytic cleavage. ω-hordothionin consists of a single polypeptide chain of 48 amino acids with a molecular mass of 5508 Da deduced from its amino acid sequence, which fully coincides with the 5508.2 Da determined by elcctrospray-ionization mass spectrometry. The isolated polypeptide showed a characteristic composition with a high content of basic amino acids (five arginine residues, two lysine residues and six histidine residues) and eight cysteine residues. and has strong sequence identity (66%) with the sorghum SIα1 α-amylase inhibitor. ω-hordothionin. like γ-hordothionin. exhibited translation inhibitory activity on both cukaryotic cell-free systems from mammalian (rat liver and rabbit reticulocyte lysates) and prokaryotic cell-free systems (Escherichia coli). However, in contrast to γ-hordothiomn, ω-hordothionin did not inhibit plant systems such as Triticum aestivum, Cucumis sativus, Vicia sativa and Hordeum vulgare. ;γ-hordothionin also inhibited the α-amylase activity from human saliva, while ω-hordothionin and the other different genetic variants of thionins, α- hordothionin and β-hordothionin. failed to show any inhibitory effect. [ABSTRACT FROM AUTHOR]
- Published
- 1996
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40. Activation of the release of dopamine in the carotid body by veratridine. Evidence for the presence of voltage-dependent Na+ channels in type I cells
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Rocher, Asunción, primary, Obeso, Ana, additional, Herreros, Benito, additional, and Gonzalez, Constancio, additional
- Published
- 1988
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41. Identification of major rye secalins as coeliac immunoreactive proteins
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Rocher, Asuncion, Calero, Miguel, Soriano, Fernando, and Mendez, Enrique
- Published
- 1996
- Full Text
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42. Hiperoxia perinatal e Hipoxia crónica como modelos experimentales para el estudio de la Transducción Hipóxica
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María Ramírez Arroyo, González, Constancio, Rocher Martín, María Asunción, Universidad de Valladolid. Facultad de Medicina, and Rocher, Asunción
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Hiperoxia ,Hipoxia ,Oxígeno - Abstract
Tesis Doctoral presentada por María Ramírez Arroyo en la Facultad de Medicina (Universidad de Valladolid) y realizada en el Instituto de Biología y Genética Molecular (CSIC).-- Sujetro a Licencia Creative Commons., [Introducción]: La hipoxia se define como una disminución de la presión de oxígeno arterial y está asociada con la ascensión a grandes alturas (denominándose a esta situación hipoxia fisiológica) o bien con patología pulmonar o coronaria. En el organismo existen varios tipos de células especializadas que detectan la hipoxia con una sensibilidad mayor que el resto del cuerpo. En este trabajo nos hemos centrado en dos de estos tipos de células: las células quimiorreceptoras del cuerpo carotídeo (CQCC) que desencadenan una hiperventilación refleja utilizando como efectores al sistema respiratorio y cardiovascular provocando un aumento de la presión de oxígeno alveolar y las células musculares lisas de las arterias pulmonares (CMLAP) que desarrollan una respuesta vasoconstrictora en el pulmón conocida como vasoconstricción pulmonar hipóxica, que redirige el flujo sanguíneo hacia las áreas mejor ventiladas y mejora el cociente ventilación-perfusión. El objetivo de este trabajo ha sido el estudio de la cascada de transducción hipóxica, tratando de dilucidar los distintos componentes así como los mecanismos implicados. Para ello se han utilizado dos modelos experimentales que tratan de simular situaciones encontradas habitualmente dentro del ámbito fisiológico o la clínica humana. El primer modelo estudiado ha sido el de la hiperoxia perinatal como analogía a la situación sufrida por los niños prematuros tratados con oxígeno suplementado y expuestos por lo tanto a grandes concentraciones del mismo, mientras que el segundo modelo, la hipoxia crónica, trata de reproducir la situación fisiológica que se produce en la ascensión a grandes alturas con concentraciones de oxígeno muy pobres por la disminución de la presión barométrica. Ambos modelos se han realizado utilizando como animal ratas wistar, variando las concentraciones de oxígeno ambiental mediante el uso de una cámara hipobárica: 55-60% O2 para el modelo de hiperoxia perinatal y 10-11%O2 para el modelo de hipoxia crónica. [Contenido de la investigación]: El contenido de este proyecto de Tesis Doctoral se centra en los resultados obtenidos en estos dos modelos experimentales. Por un lado, los datos obtenidos en el modelo de hiperoxia perinatal se centran en el estudio del estado redox de estos animales evaluado con distintos parámetros como medidas de la actividad enzimática, biomarcadores de estrés oxidativo, potencial redox de la célula¿ realizados sobre distintos tejidos de estos animales, así como el estudio de la funcionalidad del CC y de las CMLAP. Por otra parte también se ha estudiado el efecto de una dieta suplementada con antioxidantes con el propósito de evaluar si resulta beneficiosa y minimiza de algún modo el daño sufrido por estos animales. A su vez, los datos obtenidos en el modelo de hipoxia crónica, se centran con exclusividad en el cuerpo carotídeo y están encaminados al estudio de la cascada de transducción AMPc-PKA-Epac., [Conclusión]: Las conclusiones relevantes para el primer modelo serían que: La hiperoxia perinatal produce una pérdida permanente de la respuesta vasoconstrictora pulmonar cuando se evalúa en el estado adulto de estos animales, así como daño oxidativo en tejido pulmonar y hepático en etapas tempranas del desarrollo. El empleo de una dieta suplementada en antioxidantes durante el tiempo que los animales están expuestos a altas concentraciones de oxígeno permite que estos animales retengan la respuesta vasoconstrictora del pulmón, lo cual tiene una gran potencialidad clínica. Las conclusiones del segundo modelo indican que: Los animales sometidos a hipoxia crónica posee una vía de señalización AMPc-Epac que está implicada en la respuesta del CC a la hipoxia, a la acidosis y a la potenciación de ambos estímulos aplicados de forma simultánea, de modo que la proteína Epac aparece como un nuevo efector en la cascada de transducción, lo cual también ha sido confirmado mediante el análisis de su expresión directamente en las CQCC.
- Published
- 2019
43. Efectos inducidos por la hipoxia crónica intermitente en rata y cobaya como modelos animales de la apnea obstructiva del sueño
- Author
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Inmaculada Docio Cuadrado, Rocher, Asunción, Prieto-Lloret, Jesús, Rocher Martín, María Asunción, Prieto Lloret, Jesús, and Universidad de Valladolid. Facultad de Medicina
- Subjects
Hipertensión ,Apnea obstructiva del sueño ,Hipoxia ,Cuerpo carotídeo - Abstract
Doctorado en Investigación Biomédica., El cuerpo carotídeo (CC) tiene un papel fundamental en la génesis de las modificaciones que participan en el síndrome de apnea obstructiva del sueño debido a la activación y sensibilización de este órgano quimiorreceptor por la hipoxia crónica intermitente (HCI). Dichos fenómenos conducen a la activación secuencial de centros nerviosos troncoencefálicos y del simpático que tratarán de mantener la homeostasis del organismo al aumentar la ventilación y generar una respuesta vasopresora. Sin embargo, su activación permanente produce efectos adversos que conducen a la hipertensión sistémica. Por otra parte, otros mecanismos independientes de la sensibilización del CC se han propuesto como mecanismos patogénicos que también conducen a la hipertensión a través fundamentalmente de la disfunción endotelial. En esta tesis se han utilizado dos modelos animales de HCI, rata joven y vieja y cobaya joven, con el objetivo de avanzar en el conocimiento sobre los efectos de la HCI mediados y no mediados por el CC. Los principales resultados encontrados en el modelo de HCI de rata joven y vieja son la sensibilización del CC similar en ambas edades después de 15 días de exposición a HCI. Estos resultados no se correlacionan con una sensibilización del reflejo respiratorio, medido como aumento de la respuesta ventilatoria hipóxica en ninguna de las edades analizadas. Las ratas jóvenes muestran una alteración hemodinámica presentando hipertensión. Estos resultados se ajustan en parte a las características de los pacientes que sufren AOS, los cuales muestran un aumento en la respuesta respiratoria y una actividad nerviosa simpática elevada frente a la hipoxia aguda, lo que les hace propensos a desarrollar hipertensión sistémica. El envejecimiento produce un declive gradual en la función de los órganos y sistemas corporales; en este sentido la edad per se en las ratas produce hipertensión sin que la HCI lo modifique. Estos animales presentan una tendencia a sufrir disfunción endotelial en la arteria carótida que se ve agravada por la exposición a HCI. Aunque a nivel morfológico no se observan diferencias inducidas por la HCI, el envejecimiento en las ratas conduce a un aumento en el grosor del vaso arterial. Nuestros datos indican que la pérdida de la homeostasis por la edad prevalece manteniendo en un segundo plano los efectos perjudiciales de la HCI. Los principales resultados encontrados en el modelo de HCI de cobaya son la falta de sensibilización del CC después de la exposición a HCI durante 30 días y, como consecuencia, la falta de respuesta respiratoria refleja a la hipoxia aguda (excepto a hipoxia muy intensa), la cual se ha descrito en otros roedores cuyo CC es sensible a la hipoxia. Desde un enfoque integrador, que combina estudios funcionales in vivo e in vitro, hemos probado la hipótesis de que el efecto hipertensivo arterial sistémico de la HCI se eliminaría o atenuaría por la falta de capacidad de respuesta del CC en cobayas. Nuestros datos apoyan parcialmente esta hipótesis, mostrando que los cobayas, comparados con las ratas, tienen un cambio muy pequeño de presión arterial sistémica después de la HCI, a pesar de que se producen efectos simpáticos en ambos; esto sugiere un papel crítico de los mecanismos de detección de oxígeno en el CC para la sensibilización inducida por HCI. Además, queda descartado que el aumento en la presión arterial observado después de la HCI en el cobaya se deba en parte a mecanismos independientes del reflejo quimiorreceptor como la disfunción endotelial puesto que ni las propiedades vasculares medidas como contracción y relajación del vaso ni lo factores vasoactivos medidos en plasma, se alteraron en los cobayas tras la exposición a HCI.
- Published
- 2019
44. Dimorfismo sexual en un modelo de hipertensión pulmonar en rata
- Author
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Moral Alonso, María, Rocher Martín, María Asunción, Olea Fraile, Elena, Universidad de Valladolid. Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid. Facultad de Medicina, Rocher, Asunción, and Olea, Elena
- Subjects
Hipertensión arterial pulmonar ,Resistencia vascular pulmonar ,Dimorfismo sexual ,Muerte prematura - Abstract
La hipertensión arterial pulmonar (HAP) se caracteriza por el aumento progresivo de la resistencia vascular pulmonar (RVP) que conduce al fallo del ventrículo derecho y puede llegar a provocar la muerte prematura; se considera hipertensión cuando la presión media en la arteria pulmonar es igual o superior a 25mmHg en reposo. Puede estar ocasionada por múltiples patologías como la enfermedad veno-oclusiva pulmonar, hipertensión pulmonar persistente del recién nacido (HPPRN), cardiopatía izquierda o trastornos pulmonares que producen hipoxemia, causa en la que va a estar centrado este trabajo. Entre otros factores que pueden ocasionar esta enfermedad podemos encontrar también la predisposición genética (mutación en el gen que afecta la expresión del receptor BMPR2), la inducción por fármacos o asociada a otras patologías que obstruyen la microcirculación pulmonar como trastornos del tejido conectivo, VIH, hipertensión portal o cardiopatías congénitas., Departamento de Bioquímica y Biología Molecular y Fisiología, Máster en Investigación Biomédica
- Published
- 2017
45. Estudio comparativo del control respiratorio y de la defensa frente a la hipoxia mediados por el cuerpo carotídeo en cobaya y rata
- Author
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Elvira González Obeso, Rocher Martín, María Asunción, Gómez Niño, María Ángeles, Universidad de Valladolid. Facultad de Ciencias, Gómez-Niño, A., and Rocher, Asunción
- Subjects
Respiratorio, Aparato-Fisiología ,Hipoxia - Abstract
Tesis Doctoral presentada por Elvira González Obeso para optar al grado de Doctor por la Universidad de Valladolid, Facultad de Medicina (Departamento de Bioquímica y Biología y Fisiología).-- Sujeta a Licencia Creative Commons., Se presenta un estudio compartativo morfológico y funcional del cuerpo carotídeo de cobaya, caracterizado por completo por primera vez en este trabajo de Tesis Doctoral, con el de la rata, que está bien caracterizado. El cobaya posee un cuerpo carotídeo hipotrófico comparado con el de rata. La exposición a hipoxia crónica no modificó el tamaño del cuerpo carotídeo en el cobaya pero duplicó el de rata. La cantidad de células tirosina hidroxilasa positivas en cobaya es menor que en rata (11% frente a 45% en cultivos primarios). Los parámetros ventilatorios basales en cobaya y en rata son comparables. El cobaya no hiperventila en respuesta a hipoxia aguda (10% O2) y el mismo estímulo duplica el volumen minuto en rata. En ambas especies la estimulación hipercápnica duplicó el volumen ventilatorio por minuto. Esto implica que la detección/transducción de la hipoxia a nivel del cuerpo carotídeo, o algún otro elemento del arco reflejo quimiorreceptor responsable de las respuestas ventilatorias a la hipoxia, no son funcionales en el cobaya. También se comprobó que el proceso de aclimatación a la hipoxia sostenida, que es mediado por el cuerpo carotídeo, no opera en el cobaya. Se estudió toda la cascada de trasducción del estímulo hipóxico en las células quimiorreceptoras de cobaya, comparándolas con las de rata. Se comprobó que las células quimiorreceptoras de cobaya no son activadas por la hipoxia. Sin embargo la respuesta al alto K+ extracelular demuestra que la maquinaria exocitótica de las células quimiorreceptoras del cobaya es normal. Por tanto, la incapacidad para responder a la hipoxia puede deberse a que este estímulo no es detectado por las células quimiorreceptoras de cobaya o a que algún elemento específico del acoplamiento estímulo-secrección para el estímulo hipóxico no se experesa en esta especie. El conjunto de nuestros hallazgos indican que la hipoxia no es un estímulo eficaz para las células quimiorreeptoras del cobaya, debido a que o las células no expresan el "sensor de O2" o el factor de acoplamiento entre el sensor y los canales de K+.
- Published
- 2014
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