Person:
Recio Visedo, María Paz

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María Paz
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Recio Visedo
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https://hdl.handle.net/20.500.14352/77495
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Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Fisiología
Area
Fisiología
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    Role of neuronal voltage‐gated K+ channels in the modulation of the nitrergic neurotransmission of the pig urinary bladder neck
    (British Journal of Pharmacology, 2008) Hernández Martín, Marina; Barahona Gomáriz, María Victoria; Recio Visedo, María Paz; Navarro Dorado, Jorge; Bustamante Alarma, Salvador; Benedito Castellote, Sara; García Sacristán, Albino; Prieto Ocejo, Dolores; Orensanz Muñoz, Luis Miguel
    Background and purpose: As nitric oxide (NO) plays an essential role in the inhibitory neurotransmission of the bladder neck of several species, the current study investigates the mechanisms underlying the NO‐induced relaxations in the pig urinary bladder neck. Experimental approach:Urothelium‐denuded bladder neck strips were dissected and mounted in isolated organ baths containing a physiological saline solution at 37 °C and continuously gassed with 5% CO2and 95% O2, for isometric force recording. The relaxations to transmural nerve stimulation (EFS), or to exogenously applied acidified NaNO solution were carried out on strips pre‐contracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively. Key results:EFS (0.2–1 Hz) and addition of acidified NaNO solution (1 μM–1 mM) evoked frequency‐ and concentration‐dependent relaxations, respectively. These responses were potently reduced by the blockade of guanylate cyclase and were not modified by the K+ channel blockers iberiotoxin, charybdotoxin, apamin or glibenclamide. The voltage‐gated K+ (Kv) channels inhibitor 4‐aminopyridine, greatly enhanced the nitrergic relaxations evoked by EFS, but did not affect the NaNO2 solution‐induced relaxations. Conclusions and implications:NO, whose release is modulated by pre‐junctional Kv channels, relaxes the pig urinary bladder neck through a mechanism dependent on the activation of guanylate cyclase, in which post‐junctional K+ channels do not seem to be involved. Modulation of Kv channels could be useful in the therapy of the urinary incontinence produced by intrinsic sphincteric deficiency.
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    Project number: 292
    Implementación del aprendizaje basado en problemas (ABP) en la enseñanza práctica de la fisiología del sistema digestivo
    (2019) López-Oliva Muñoz, María Elvira; Sánchez Pina, Ana Alejandra; Hernández Rodríguez, Medardo Vicente; Prieto Ocejo, Dolores; García Sacristán, Albino; Contreras Jiménez, Cristina; Martínez Gómez, Ana Cristina; Agis Torres, Angel; Climent Florez, Belén; Rivera de los Arcos, Luis; Recio Visedo, María Paz; Benedito Castellote, Sara; Muñoz Picos, Mercedes; Raposo González, Rafaela
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    Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries
    (Naunyn Schmiedebergs Arch Pharmacol, 2011) Fernandes, Vítor S.; Martínez Sáenz, Ana; Recio Visedo, María Paz; Fernandes Ribeiro, Ana Sofía; Ana Sánchez; Martínez Sainz, María Del Pilar; Martínez Gómez, Ana Cristina; García Sacristán, Albino; Orensanz Muñoz, Luis Miguel; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16 Hz) and exogenous SNAP (0.1-30 μM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1 nM-10 μM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.
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    Noradrenergic vasoconstriction of pig prostatic small arteries
    (Naunyn-Schmiedeberg’s Arch Pharmacol, 2008) Recio Visedo, María Paz; Orensanz Muñoz, Luis Miguel; Martínez Sainz, María Del Pilar; Navarro Dorado, Jorge; Bustamante Alarma, Salvador; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    The current study investigated the distribution of adrenergic nerves and the action induced by noradrenaline (NA) in pig prostatic small arteries. Noradrenergic innervation was visualized using an antibody against dopamine-beta-hydroxylase (DBH), and the NA effect was studied in small arterial rings mounted in microvascular myographs for isometric force recordings. DBH-immunoreactive nerve fibers were located at the adventitia and the adventitia-media border of the vascular wall. Electrical field stimulation (EFS, 1-32 Hz) evoked frequency-dependent contractions that were reduced by guanethidine and prazosin (adrenergic neurotransmission and α1-adrenoceptors blockers, respectively) and by the α2-adrenoceptor agonist UK 14,304. The α2-adrenoceptor antagonist rauwolscine reversed the UK 14,304-produced inhibition. NA produced endothelium-independent contractions that were antagonized with low estimated affinities and Schild slopes different from unity by prazosin and the α1A-adrenoceptor antagonist N-[2-(2-cyclopropylmethoxyphenoxy) ethyl]-5-chloro-α-α-dimethyl-1H-indole-3-ethanamine (RS 17053). The α1A-adrenoceptor antagonist 5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione (RS 100329), which also displays high affinity for α1L-adrenoceptors, and the α1L-adrenoceptor antagonist tamsulosin, which also has high affinity for α1A- and α1D-adrenoceptors, induced rightward shifts with high affinity of the contraction-response curve to NA. The α1D-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]8-azaspiro[4,5]decane-7,9-dione dihydrochloride (BMY 7378) failed to modify the NA contractions that were inhibited by extracellular Ca2+ removal and by voltage-activated (L-type) Ca2+ channel blockade. These data suggest that pig prostatic resistance arteries have a rich noradrenergic innervation; and NA, whose release is modulated by prejunctional α2-adrenoceptors, evokes contraction mainly through activation of muscle α1L-adrenoceptors coupled to extracellular Ca2+ entry via voltage (L-type)- and non-voltage-activated Ca2+ channels.
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    Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle
    (Neurourology and urodynamics, 2013) Ribeiro, Ana Sofía Fernandes; Leite Fernandes, Vitor Samuel; Martínez Sainz, María Del Pilar; Martínez-Sáenz, Ana; Pazos Rodríguez, María Ruth; Orensanz Muñoz, Luis Miguel; Recio Visedo, María Paz; Bustamante Alarma, Salvador; Carballido Rodríguez, Joaquín; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Aims: The current study investigates the role played by bradykinin (BK) receptors in the contractility to the pig bladder neck smooth muscle. Methods: Bladder neck strips were mounted in myographs for isometric force recordings and BK receptors expression was also determined by immunohistochemistry. Results: B2 receptor expression was observed in the muscular layer and urothelium whereas B1 expression was consistent detected in urothelium. A strong B2 immunoreactivity was also observed within nerve fibers among smooth muscle bundles. On urothelium-denuded preparations basal tone, BK induced concentration-dependent contractions which were reduced in urothelium-intact samples, by extracellular Ca(2+) removal and by blockade of B2 receptors and voltage-gated Ca(2+) (VOC) and non-VOC channels, and increased by cyclooxygenase (COX) inhibition. On phenylephrine-precontracted denuded strips, under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. In urothelium-intact samples, the B1 receptor agonist kallidin promoted concentration-dependent relaxations which were reduced by blockade of B1 receptors, COX, COX-1 and large-conductance Ca(2+) -activated K(+) (BKCa ) channels and abolished in urothelium-denuded samples and in K(+) -enriched physiological saline solution-precontracted strips. Conclusions: These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated.
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    Project number: 407
    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) 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.
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    Role of endogenous hydrogen sulfide in nerve-evoked relaxation of pig terminal bronchioles
    (Pulmonary Pharmacology & Therapeutics, 2016) Fernandes, Vítor S.; Recio Visedo, María Paz; López-Oliva Muñoz, María Elvira; Martínez Sainz, María Del Pilar; Fernandes Ribeiro, Ana Sofía; Barahona Gomáriz, María Victoria; Martínez Gómez, Ana Cristina; Benedito Castellote, Sara; Agis Torres, Ángel; Cabañero, Alberto; Muñoz, Gemma M.; García Sacristán, Albino; Orensanz Muñoz, Luis Miguel; Hernández Rodríguez, Medardo Vicente
    Hydrogen sulfide (H2S) is a gasotransmitter employed for intra- and inter-cellular communication in almost all organ systems. This study investigates the role of endogenous H2S in nerve-evoked relaxation of pig terminal bronchioles with 260 μm medium internal lumen diameter. High expression of the H2S synthesis enzyme cystathionine γ-lyase (CSE) in the bronchiolar muscle layer and strong CSE-immunoreactivity within nerve fibers distributed along smooth muscle bundles were observed. Further, endogenous H2S generated in bronchiolar membranes was reduced by CSE inhibition. In contrast, cystathionine β-synthase expression, another H2S synthesis enzyme, however was not consistently detected in the bronchiolar smooth muscle layer. Electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked smooth muscle relaxation. Inhibition of CSE, nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and of ATP-dependent K+, transient receptor potential A1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels reduced the EFS relaxation but failed to modify the GYY4137 response. Raising extracellular K+ concentration inhibited the GYY4137 relaxation. Large conductance Ca2+-activated K+ channel blockade reduced both EFS and GYY4137 responses. GYY4137 inhibited the contractions induced by histamine and reduced to a lesser extent the histamine-induced increases in intracellular [Ca2+]. These results suggest that relaxation induced by EFS in the pig terminal bronchioles partly involves the H2S/CSE pathway. H2S response is produced via NO/sGC-independent mechanisms involving K+ channels and intracellular Ca2+ desensitization-dependent pathways. Thus, based on our current results H2S donors might be useful as bronchodilator agents for the treatment of lung diseases with persistent airflow limitation, such as asthma and chronic obstructive lung disease.
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    The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum
    (Biochemical Pharmacology, 2023) 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.
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    Mechanisms involved in testosterone-induced vasodilatation in pig prostatic small arteries
    (Life Sciences, 2008) Navarro Dorado, Jorge; Orensanz Muñoz, Luis Miguel; Recio Visedo, María Paz; Bustamante Alarma, Salvador; Benedito Castellote, Sara; Martínez Gómez, Ana Cristina; García Sacristán, Albino; Prieto Ocejo, Dolores; Hernández Rodríguez, Medardo Vicente
    Aims: Testosterone is beneficial to the cardiovascular system due to its direct coronary vasodilatory action and its circulatory deficiency is associated with coronary artery disease (CAD), which has been proposed as an extrinsic risk factor for benign prostatic hyperplasia (BPH). Therefore, the current study investigated the mechanisms involved in the testosterone-induced vasodilatation in pig prostatic small arteries. Main methods: The testosterone vasoactive effects were assessed in small arterial rings mounted in micro- vascular myographs for isometric force recordings. Key findings: Testosterone and the non-aromatizable metabolite 4, 5α-dihydrotestosterone (DHT) evoked a similar concentration-dependent relaxation on noradrenaline (NA)-precontracted rings. Similar responses were obtained in preparations contracted with 60 mM K+-enriched physiological saline solution. Endothelium mechanical removal or pre-treatment with blockers of nitric oxide (NO) synthase, guanylate cyclase, aromatase activity, intracellular androgenic receptor (AR), 5α-reductase, prostanoid synthesis and K+ channels, failed to modify the responses to testosterone. In Ca2+-free 124 mM KPSS, testosterone markedly inhibited in a concentration-dependent manner the contraction curve t °CaCl2. In arteries pretreated with an L-type voltage-activated Ca2+ channels (VOCCs) inhibitor, nifedipine, testosterone still relaxed noradrenaline- precontracted arteries. Significance: These data suggest that testosterone induces a direct vasodilatory action in pig prostatic small arteries independent of either endothelium, NO, prostanoids, aromatase or 5α-reductase activities, AR or K+ channels. Such an effect is suggested to be produced via blockade of extracellular Ca2+ entry through L-type VOCCs and non-L-type Ca2+ channels. Testosterone-induced vasodilatation could be useful to prevent prostatic ischemia.
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    Endogenous Hydrogen Sulfide has a Powerful Role in Inhibitory Neurotransmission to the Pig Bladder Neck
    (Journal of Urology, 2013) Leite Fernandes, Vitor Samuel; Ribeiro, Ana S.F.; Martínez, María Pilar; Orensanz, Luis M.; Barahona Gomáriz, 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.