Person:
Leite Fernandes, Vitor Samuel

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First Name
Vitor Samuel
Last Name
Leite Fernandes
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Fisiología
Area
Fisiología
Identifiers
UCM identifierORCIDScopus Author IDWeb of Science ResearcherIDDialnet IDGoogle Scholar ID

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Now showing 1 - 10 of 11
  • Publication
    Autoevaluación, Coevaluación y el uso de las TIC como enfoque innovador en las prácticas de Fisiopatología y su efecto en el proceso de enseñanza-aprendizaje del alumno
    (2023-07-31) Leite Fernandes, Vitor Samuel; Agis Torres, Ángel; Benedito Castellote, Sara; Climent Flórez, Belén; Contreras Jiménez, Cristina; García Sacristán, Albino; Gómez del Val, Alfonso; Hernández Rodríguez, Medardo Vicente; Hernández Martín, Marina; López-Oliva Muñoz, María Elvira; Merino Martín, José Joaquín; Montenegro Álvarez De Tejera, María Pilar; Muñoz Picos, Mercedes; Navarro Dorado, Jorge; Pascual Gómez, Natalia Fernanda; Perales Calvo, Manuel; Prieto Ocejo, Dolores; Puente Maya, Francisco Jesus; Raposo González, Rafaela; Recio Visedo, María Paz; Rivera De Los Arcos, Luis; Sánchez Pina, Ana Alejandra
    En las últimas décadas, la educación universitaria ha evolucionado hacia un enfoque constructivista en consonancia con las recomendaciones del Espacio Europeo de Educación Superior (EEES). En este paradigma, los estudiantes asumen un papel activo en el proceso de enseñanza-aprendizaje, mientras los profesores actúan como facilitadores. Las metodologías constructivistas fomentan el desarrollo tanto individual como grupal de competencias específicas y genéricas, al tiempo que permiten la inclusión de agentes de evaluación formativa para estimular la crítica y la autocrítica del alumno en su desempeño. En este contexto, surge la necesidad de aplicar el constructivismo a la evaluación, involucrando al estudiante en su propio proceso de evaluación. La autoevaluación y la coevaluación emergen como alternativas concretas para lograrlo. La autoevaluación implica que el estudiante analice y valore de manera sistemática su trabajo durante el proceso de aprendizaje para mejorar resultados y fomentar la autocrítica. Por otro lado, la coevaluación es una evaluación entre compañeros que permite valorar la implicación y actitud de los miembros del grupo, estimulando el aprendizaje colectivo. Las Tecnologías de la Información y Comunicación (TIC) juegan un papel importante en la educación y en la evaluación de los alumnos, diferenciándose de las prácticas tradicionales. La implementación de TIC no solo desarrolla habilidades en el proceso enseñanza-aprendizaje, sino también favorece la autoevaluación y la coevaluación. Con base en este enfoque, se presenta un proyecto de innovación docente en la asignatura de Fisiopatología para estudiantes de Farmacia. Los alumnos crearán videos sobre temas específicos de la práctica y se evaluarán a sí mismos y a sus compañeros utilizando la herramienta App Plickers. Sin embargo, aún no existe una metodología claramente definida para la implementación de estrategias constructivistas y uso de TIC en Fisiopatología, destacando la importancia y relevancia de este proyecto.
  • Publication
    Phosphodiesterase type 4 inhibition enhances nitric oxide- and hydrogen sulfide-mediated bladder neck inhibitory neurotransmission
    (Nature Research, 2018-03-16) Agis Torres, Ángel; Recio Visedo, María Paz; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Barahona Gomáriz, María Victoria; Benedito Castellote, Sara; Bustamante, Salvador; Jiménez-Cidre; Miguel Ángel; García Sacristán, Albino; Prieto Ocejo, Dolores; Leite Fernandes, Vitor Samuel; Hernández Rodríguez, Medardo Vicente
    Nitric oxide (NO) and hydrogen sulfide (H2S) play a pivotal role in nerve-mediated relaxation of the bladder outflow region. In the bladder neck, a marked phosphodiesterase type 4 (PDE4) expression has also been described and PDE4 inhibitors, as rolipram, produce smooth muscle relaxation. This study investigates the role of PDE4 isoenzyme in bladder neck gaseous inhibitory neurotransmission. We used Western blot and double immunohistochemical staining for the detection of NPP4 (PDE4) and PDE4A and organ baths for isometric force recording to roflumilast and tadalafil, PDE4 and PDE5, respectively, inhibitors in pig and human samples. Endogenous H2S production measurement and electrical field stimulation (EFS) were also performed. A rich PDE4 and PDE4A expression was observed mainly limited to nerve fibers of the smooth muscle layer of both species. Moreover, roflumilast produced a much more potent smooth muscle relaxation than that induced by tadalafil. In porcine samples, H2S generation was diminished by H2S and NO synthase inhibition and augmented by roflumilast. Relaxations elicited by EFS were potentiated by roflumilast. These results suggest that PDE4, mainly PDE4A, is mostly located within nerve fibers of the pig and human bladder neck, where roflumilast produces a powerful smooth muscle relaxation. In pig, the fact that roflumilast increases endogenous H2S production and EFS-induced relaxations suggests a modulation of PDE4 on NO- and H2S-mediated inhibitory neurotransmission.
  • Publication
    The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum
    (Elsevier, 2023-09) Navarro Dorado, Jorge; Climent Flórez, Belén; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Hernández Martín, Marina; Agis Torres, Ángel; Recio Visedo, María Paz; Barahona Gomáriz, María Victoria; Benedito Castellote, Sara; Leite Fernandes, Vitor Samuel; Hernández Rodríguez, Medardo Vicente
    Bitter taste receptors (TAS2R) are found in numerous extra-oral tissues, including smooth muscle (SM) cells in both vascular and visceral tissues. Upon activation, TAS2R stimulate the relaxation of the SM. Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway is involved in penile erection, and type 5 phosphodiesterase (PDE5) inhibitors, a cGMP-specific hydrolase are used as first-line treatments for erectile dysfunction (ED). Nevertheless, PDE5 inhibitors are ineffective in a considerable number of patients, prompting research into alternative pharmacological targets for ED. Since TAS2R agonists regulate SM contractility, this study investigates the role of TAS2Rs in rat corpus cavernosum (CC). We performed immunohistochemistry to detect TAS2R10, isometric force recordings for TAS2R agonists denatonium and chloroquine, the slow-release H2S donor GYY 4137, the NO donor SNAP, the β-adrenoceptor agonist isoproterenol and electrical field stimulation (EFS), as well as measurement of endogenous hydrogen sulfide (H2S) production. The immunofluorescence staining indicated that TAS2R10 was broadly expressed in the CC SM and to some extent in the nerve fibers. Denatonium, chloroquine, SNAP, and isoproterenol cause potent dose-dependent SM relaxations. H2S production was decreased by NO and H2S synthase inhibitors, while it was enhanced by denatonium. In addition, denatonium increased the relaxations induced by GYY 4137 and SNAP but failed to modify EFS- and isoproterenol-induced responses. These results suggest neuronal and SM TAS2R10 expression in the rat CC, where denatonium induces a strong SM relaxation per se and promotes the H2S- and NO-mediated inhibitory gaseous neurotransmission. Thus, TAS2R10 might represent a valuable therapeutic target in ED.
  • Publication
    Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide
    (Hindawi, 2019-08-20) Blaha, Igor; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Recio Visedo, María Paz; Agis Torres, Ángel; Martínez Gómez, Ana Cristina; Benedito Castellote, Sara; García Sacristán, Albino; Leite Fernandes, Vitor Samuel; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Purpose: This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and methods: Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results: Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions: These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.
  • Publication
    Endogenous Hydrogen Sulfide has a Powerful Role in Inhibitory Neurotransmission to the Pig Bladder Neck
    (Baltimore : Lippincott Williams & Wilkins, 2013-04-01) Leite Fernandes, Vitor Samuel; Ribeiro, Ana S.F.; Martínez, María Pilar; Orensanz, Luis M.; Barahona, María Victoria; Martínez-Sáenz, Ana; Recio Visedo, María Paz; Benedito Castellote, Sara; Bustamante, Salvador; Carballido, Joaquín; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Purpose: We investigated the possible involvement of H2S in nitric oxide independent inhibitory neurotransmission to the pig bladder neck. Materials and methods: We used immunohistochemistry to determine the expression of the H2S synthesis enzymes cystathionine γ-lyase and cystathionine β-synthase. We also used electrical field stimulation and myographs for isometric force recordings to study relaxation in response to endogenously released or exogenously applied H2S in urothelium denuded, phenylephrine precontracted bladder neck strips under noradrenergic, noncholinergic, nonnitrergic conditions. Results: Cystathionine γ-lyase and cystathionine β-synthase expression was observed in nerve fibers in the smooth muscle layer. Cystathionine γ-lyase and cystathionine β-synthase immunoreactive fibers were also identified around the small arteries supplying the bladder neck. Electrical field stimulation (2 to 16 Hz) evoked frequency dependent relaxation, which was decreased by DL-propargylglycine and abolished by tetrodotoxin (blockers of cystathionine γ-lyase and neuronal voltage gated Na(+) channels, respectively). The cystathionine β-synthase inhibitor O-(carboxymethyl)hydroxylamine did not change nerve mediated responses. The H2S donor GYY4137 (0.1 nM to 10 μM) induced potent, concentration dependent relaxation, which was not modified by neuronal voltage gated Na(+) channels, or cystathionine γ-lyase or cystathionine β-synthase blockade. Conclusions: Results suggest that endogenous H2S synthesized by cystathionine γ-lyase and released from intramural nerves acts as a powerful signaling molecule in nitric oxide independent inhibitory transmission to the pig bladder neck.
  • Publication
    Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.
    (Lippincott Williams & Wilkins, 2013-08-01) Leite Fernandes, Vitor Samuel; Fernandes Ribeiro, Ana Sofía; Barahona Gomáriz, María Victoria; Orensanz Muñoz, Luis Miguel; Martínez Sáenz, Ana; Recio Visedo, María Paz; Martínez Gómez, Ana Cristina; Bustamante, Salvador; Carballido, Joaquín; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Purpose: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. Materials and methods: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. Results: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). Conclusions: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation. Keywords: 4-AP; 4-aminopyridine; AM; ATP; ATP dependent K(+); CGRP; COX; CSE; CSPA; Ca(2+) activated K(+); Emax; K(ATP); K(Ca); K(V); KPSS; L-NOARG; MLCP; N(G)-nitro-L-arginine; NO; PACAP; PKA; PSS; TRPA(1); TRPV(1); VOC; VPAC; [Ca(2+)](i); acetoxymethyl ester; adenosine 5′-triphosphate; calcitonin gene-related peptide; capsaicin sensitive primary afferent; cyclooxygenase; cystathionine γ-lyase; hydrogen sulfide; intracellular Ca(2+); maximum response; muscle, smooth; myosin light chain phosphatase; nitric oxide; physiological saline solution; pituitary adenylyl cyclase activating polypeptide; potassium channels; potassium rich PSS; protein kinase A; synaptic transmission; transient receptor potential A1; transient receptor potential vanilloid 1; urinary bladder; vasoactive intestinal peptide receptor; voltage gated Ca(2+); voltage gated K(+).
  • Publication
    Stop Hipertensión con APS/UCM I
    (2023-06-30) López-Oliva Muñoz, Mª Elvira; Sánchez Pina, Ana A.; Hernández Martín, Marina; Rivera de los Arcos, Luis; López-Calderón Barreda, Asunción; Paredes Royano, Sergio Damián; Vicente Torres, Mª Ángeles; de las Heras Jiménez, Natalia; Benedito Castellote, Sara; Prieto Ocejo, Dolores; Issa García, Jousef Ángel; García Donaire, José Antonio; Abad Cardiel, María; Martell Claros, Nieves; Gómez Garre, María Dulcenombre; Azcutia Criado, Verónica; Contreras Jiménez, Cristina; Redondo Castillejo, Rocío; Hurtado Carneiro, Verónica; Rodrígues Díez, Raquel; Cachofeiro Ramos, Victoria; Montenegro Álvarez de Tejera, Mª Pilar; Das Chagas Vasconcelos de Sousa Neto, Francisco; Gómez del Val, Alfonso; Bravo San Pedro, José Manuel; Colino Galian, Belén; Fernández García, Maria José; Flóres Alcázar, Rocío; Rodríguez Ramiro, Ildefonso; Agis Torres, Ángel; García-Baró López, José Antonio; Gredilla Díaz, Ricardo; Hernández Rodríguez, Medardo V.; Leite Fernandes, Vitor Samuel; Lozano Estevan, Carmen; Martín Velasco, Ana Isabel; Martínez Martínez, Ernesto; Moreno Rupérez, Álvaro; Muñoz Picos, Mercedes; Navarro Dorado, Jorge; Nebot Valenzuela, Elena; Pascual Gómez, Natalia F.; Perales Calvo, Manuel; Priego Cuadra, Teresa; Puente Maya, Francisco Jesús; Raposo González. Rafaela; Recio Visedo, Mª Paz; Sánchez-Aguilera López. Alberto; Sancho González, María; Segovia Camargo, Gregorio; Soriano Amador, Cristina
    El Proyecto Stop Hipertensión con ApS/UCM pretende aportar nuestro granito de arena a la lucha contra la hipertensión arterial (HTA), utilizando una herramienta educativa de aprendizaje en servicio (ApS), que permita a los estudiantes de los Grados en ciencias de la salud de la UCM aprender a la vez que realizan un servicio público. La hipertensión arterial (HTA) es un problema de salud pública y un importante factor de riesgo de padecer enfermedades cardiovasculares (ECV). Su diagnóstico está determinado por la medida de la presión arterial (PA) por lo que es de extrema importancia asegurar una medida fiable y válida. La automedida de la PA (AMPA) consiste en la medida de la PA por el propio paciente o un familiar, habitualmente en su domicilio, y es una herramienta útil para el diagnóstico y control de la HTA. Pero ¿sabemos medirnos de forma correcta la PA? ¿Usamos bien los tensiómetros? ¿Sabemos interpretar los registros de la PA y cuándo consultar al médico? Realizar AMPA correctamente no es fácil y exige un esfuerzo extraordinario de recursos humanos y económicos por parte de los profesionales de Atención Primaria. Por ello son necesarias nuevas estrategias para capacitar a la población en AMPA. Con este Proyecto nos proponemos luchar contra la HTA a través de la metodología educativa de aprendizaje-servicio que combina objetivos académicos con el servicio comunitario. El alumnado de los grados de Ciencias de la Salud de la UCM forman a la población en la correcta AMPA, asesorándoles sobre el uso correcto de los tensiómetros, enseñándoles a interpretar los resultados y alertándoles de cuándo acudir al médico. En el curso 2022-2023, el servicio público se ha dirigido principalmente al colectivo de mayores por ser especialmente vulnerables a padecer ECV en los Ayuntamientos de Coslada, Alcobendas y Alcorcón, y en las residencias Afanias y Neurovida, y a la población general que acuda a la Facultad durante la Semana de la Ciencia CAM/UCM 2022, a la Feria de la Salud de Coslada y a la campaña contra la HTA de la UCM junto con el Servicio de Medicina del Trabajo. Hemos demostrado que este proyecto es una herramienta rentable y efectiva en la lucha contra la HTA, vinculando la salud pública, los recursos de los ayuntamientos y la universidad. Se cubre así una necesidad y servicio social que podría salvar muchas vidas con recursos de bajo costo, cumpliendo con los objetivos del desarrollo sostenible y con los objetivos de la Sociedad Española de Hipertensión (SEH-LELHA) y de la estrategia HEARTS de la OPS/OMS. Los estudiantes se dan cuenta de la realidad de la Salud pública al tener contacto directo con la población, realizando un servicio a la sociedad, y desarrollándose profesionalmente. Agrademos su colaboración a: Los ayuntamientos de Coslada, Alcorcón y Alcobendas de Madrid. Las residencias de mayores Afanias y Neurovida. Las Sociedades científicas SEH-LELHA, SECF y SEAPEC. El Dr. Orduñez, lider de la estrategia HEARTS PAHO/WHO Los colegios profesionales COFM y CODEM. Las empresas River International S.L. (Beurer) and Peroxfarma S.L. (Omrom)
  • Publication
    Adaptación a un entorno semipresencial de una nueva herramienta mixta del aprendizaje basado en problemas en combinación con las prácticas de laboratorio clínico a la nueva asignatura Bases Anatómicas y Fisiología del Cuerpo Humano
    (2021-06) Muñoz Picos, Mercedes; Agis Torres, Ángel; Benedito Castellote, Sara; Bragado Aguado, María del Carmen; Climent Flórez, Belén; Contreras Jiménez, Cristina; García Sacristán, Albino; Gómez Del Val, Alfonso; Gutiérrez Cruz, Alejandro; Hernández Rodríguez, Medardo Vicente; Leite Fernandes, Vitor Samuel; López-Oliva Muñoz, María Elvira; Montenegro Álvarez De Tejera, María Pilar; Navarro Dorado, Jorge; Perales Calvo, Manuel; Puente Maya, Francisco Jesús; Raposo González, Rafaela; Recio Visedo, María Paz; Rivera de los Arcos, Luis; Rodríguez Prados, Claudia; Sánchez Pina, Ana Alejandra
  • Publication
    Cardiac System during the Aging Process
    (California : JKL International, 2023) Fernandes Ribeiro, Ana Sofía; Egea Zerolo, Blanca; Lopez-Espuela, Fidel; Sanchez, Raul; Leite Fernandes, Vitor Samuel
    The aging process is accompanied by a continuous decline of the cardiac system, disrupting the homeostatic regulation of cells, organs, and systems. Aging increases the prevalence of cardiovascular diseases, thus heart failure and mortality. Understanding the cardiac aging process is of pivotal importance once it allows us to design strategies to prevent age-related cardiac events and increasing the quality of live in the elderly. In this review we provide an overview of the cardiac aging process focus on the following topics: cardiac structural and functional modifications; cellular mechanisms of cardiac dysfunction in the aging; genetics and epigenetics in the development of cardiac diseases; and aging heart and response to the exercise.
  • Publication
    Mechanisms involved in endothelin‐1‐induced contraction of the pig urinary bladder neck
    (Wiley, 2011-09-26) Arteaga, José Luis; Orensanz Muñoz, Luis Miguel; Martínez, María Pilar; Barahona Gomáriz, María Victoria; Recio Visedo, María Paz; Martínez‐Sáenz, Ana; Leite Fernandes, Vitor Samuel; Fernandes Ribeiro, Ana Sofía; García‐Sacristán, Albino; Prieto Ocejo, Dolores; Medardo Hernández; Hernández Rodríguez, Medardo Vicente
    AbstractAimsThere is no information about the signaling pathways involved in the endothelin‐1 (ET‐1)‐induced contraction of bladder neck. The current study investigates the mechanisms involved in the ET‐1‐elicited contraction in the pig bladder neck.MethodsBladder neck strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O2 and 5% CO2, for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ETA receptor expression was also determined, by both immunohistochemistry and Western blot.ResultsETA receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ETA‐immunoreactivity (ETA‐IR) was identified within nerve fibers among smooth muscle bundles. ET‐1 and ET‐2 evoked similar concentration‐dependent contractions of urothelium‐denuded preparations. ET‐3 produced a slight response, whereas the ETB receptor agonist BQ3020 failed to promote contraction. BMS182874, an ETA receptor antagonist, reduced ET‐1‐induced contraction whereas BQ788, an ETB antagonist, did not change such responses. ET‐1 contractions were reduced by extracellular Ca2+ removal and by inhibition of voltage‐gated Ca2+ (VOC) (L‐type) and non‐VOC channels, Rho/Rho‐kinase pathway, and neuronal VOC channels. NA produced contractions which were enhanced by ET‐1 threshold concentrations. ETA receptor blockade enhanced nitric oxide‐dependent nerve‐mediated relaxations.ConclusionsThese results suggest that ET‐1 produces contraction via muscular ETA receptors coupled to extracellular Ca2+ entry via VOC (L‐type) and non‐VOC channels. Intracellular Ca2+ mobilization and a Rho/Rho‐kinase pathway could also be involved in these responses. ET‐1‐evoked potentiation on noradrenergic contraction, and neuronal ETA receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated. Neurourol. Urodynam. 31:156–161, 2012. © 2011 Wiley Periodicals, Inc.