27 research outputs found

    Médula adrenal

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    Sección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEpu

    Eritrocitos, glóbulos rojos o hematíes

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    Sección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEpu

    Effects of bazedoxifene treatment on the bone quality of ovariectomized rats

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    Objetivo: El bazedoxifeno es un SERM de 3ª generación con efectos agonistas sobre el hueso y sobre el útero y el tejido mamario. Nuestro objetivo ha sido estudiar los efectos del bazedoxifeno sobre la calidad ósea en un modelo experimental de ratas ovariectomizadas. Material y métodos: Se utilizaron 3 grupos de 15 ratas Wistar hembras de 6 meses de edad: uno control; otro de ratas ovariectomizadas; y un tercer grupo de ratas ovariectomizadas tratadas con bazedoxifeno (0,33 mg/kg/día). Tras 8 meses se estudiaron la densitometría ósea lumbar y femoral, los parámetros microtomográficos, los marcadores bioquímicos de remodelado y los parámetros biomecánicos del hueso. Resultados: La ovariectomía descendió la densidad ósea femoral y lumbar. La última se recuperó parcialmente con bazedoxifeno. El remodelado óseo aumentó, recuperando el bazedoxifeno los niveles de formación. El bazedoxifeno recuperó la fracción volumétrica ósea (BV/TV), la densidad de superficie ósea (BS/TV), el aumento en la separación trabecular (Tb.Sp), la disminución en el número de trabéculas (Tb.N), el aumento del factor de patrón trabecular (Tb.Pf) y el índice de modelo estructural (SMI). La superficie relativa cortical aumentó tras la ovariectomía, normalizándose con bazedoxifeno. También recuperó la deformación máxima antes de la rotura producida por la ovariectomía, y amortiguó parcialmente la ganancia de peso de las ratas ovariectomizadas. Conclusiones: Nuestro estudio muestra resultados positivos del bazedoxifeno sobre la calidad ósea. Este fármaco podría estar especialmente indicado para mujeres jóvenes postmenopáusicas con osteoporosis o en riesgo de padecerla.Objetive: Bazedoxifene is a 3rd generation SERM with agonistic effects on the bones, uterus and breast tissue. Our goal has been to study the effects of bazedoxifene on bone quality of an experimental group of ovariectomized rats. Material and methods: 3 groups of 15 6‐month‐old Wistar female rats were used: a control group, a group of untreated ovariectomized rats and a group of ovariectomized rats treated with bazedoxifene (0.33 mg/kg/day). After 8 months we studied the lumbar and femur bone densitometry, the microtomographic parameters, the biochemical markers for bone remodelling and the bone biomechanical parameters. Results: The ovariectomy depleted the femur and lumbar bone density. After receiving bazedoxifene, the lumbar bone density showed partial healing. Bone remodelling increased recovering bazedoxifene formation levels. Bazedoxifene promoted the recovery of the bone volume fraction (BV/TV), the bone surface density (BS/BV), the trabecular number (Tb.N), the trabecular spacing (Tb.Sp), the trabecular pattern factor (Tb.Pf) and the structural model index (SMI). The cortical surface increased after the ovariectomy and returned to normal levels with the administration of bazedoxifene. The maximum deformation showed before the ovariectomy was also restored, partially cushioning the ovariectomized rats’ weight gain. Conclusions: Our study has shown bazedoxifene positive results on bone quality. This specific drug could be particularly suitable for young postmenopausal women suffering or at risk of suffering osteoporosis.Carlos III Health Institute,Federación Española de Enfermedades RarasSección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEpu

    Noradrenergic vasoconstriction of pig prostatic small arteries

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    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.Fundación Médica Mutua MadrileñaSección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEpu

    Role of Calcitonin Gene-Related Peptide in Inhibitory Neurotransmission to the Pig Bladder Neck

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    Purpose: We studied the role of calcitonin gene-related peptide in nonadrenergic, noncholinergic neurotransmission to the pig bladder neck. Materials and Methods: We used immunohistochemical techniques to determine the distribution of calcitonin gene-related peptide immunoreactive fibers as well as organ baths for isometric force recording. We investigated relaxation due to endogenously released or exogenously applied calcitonin gene-related peptide in urothelium denuded phenylephrine precontracted strips treated with guanethidine, atropine and NG-nitro-L-arginine to block noradrenergic neurotransmission, muscarinic receptors and nitric oxide synthase, respectively. Results: Rich calcitonin gene-related peptide immunoreactive innervation was found penetrating through the adventitia and distributed in the suburothelial and muscle layers. Numerous, variable size, varicose calcitonin gene-related peptide immunopositive terminals were seen close below the urothelium. In the muscle layer calcitonin gene-related peptide immunopositive nerves usually appeared as varicose terminals running along muscle fibers. Electrical field stimulation (2 to 16 Hz) and exogenous calcitonin gene-related peptide (0.1 nM to 0.3 μM) evoked frequency and concentration dependent relaxation, respectively. Nerve responses were potentiated by capsaicin, decreased by calcitonin gene-related peptide (8–37) and abolished by tetrodotoxin, capsaicin sensitive primary afferent blockers, calcitonin gene-related peptide receptors and neuronal voltage gated Na+ channels. Calcitonin gene-related peptide-induced relaxation was potentiated by the neuronal voltage gated Ca2+ channels blocker ω-conotoxin-GVIA and decreased by calcitonin gene-related peptide (8–37). Calcitonin gene-related peptide relaxation was not modified by blockade of endopeptidases, nitric oxide synthase, guanylyl cyclase and cyclooxygenase. Conclusions: Results suggest that calcitonin gene-related peptide is involved in the nonadrenergic, noncholinergic inhibitory neurotransmission of the pig bladder neck, producing relaxation through neuronal and muscle calcitonin gene-related peptide receptors. Nitric oxide/cyclic guanosine monophosphate and cyclooxygenase pathways do not seem to be involved in such responses.Ministerio de Ciencia e Innovación, SpainSección Deptal. de Fisiología (Farmacia)Fac. de FarmaciaTRUEpu
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