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Mechanisms involved in endothelin‐1‐induced contraction of the pig urinary bladder neck
Author(s) -
Arteaga José Luis,
Orensanz Luis M.,
Martínez María Pilar,
Barahona María Victoria,
Recio Paz,
MartínezSáenz Ana,
Fernandes Vítor S.,
Ribeiro Ana S. F.,
GarcíaSacristán Albino,
Prieto Dolores,
Hernández Medardo
Publication year - 2012
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.21187
Subject(s) - medicine , contraction (grammar) , urology , endothelin receptor , endothelin 1 , urinary bladder , urinary system , neck of urinary bladder , animal study , surgery , receptor
Aims There 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. Methods Bladder neck strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O 2 and 5% CO 2 , for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ET A receptor expression was also determined, by both immunohistochemistry and Western blot. Results ET A receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ET A ‐immunoreactivity (ET A ‐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 ET B receptor agonist BQ3020 failed to promote contraction. BMS182874, an ET A receptor antagonist, reduced ET‐1‐induced contraction whereas BQ788, an ET B antagonist, did not change such responses. ET‐1 contractions were reduced by extracellular Ca 2+ removal and by inhibition of voltage‐gated Ca 2+ (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. ET A receptor blockade enhanced nitric oxide‐dependent nerve‐mediated relaxations. Conclusions These results suggest that ET‐1 produces contraction via muscular ET A receptors coupled to extracellular Ca 2+ entry via VOC (L‐type) and non‐VOC channels. Intracellular Ca 2+ mobilization and a Rho/Rho‐kinase pathway could also be involved in these responses. ET‐1‐evoked potentiation on noradrenergic contraction, and neuronal ET A receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated. Neurourol. Urodynam. 31:156–161, 2012. © 2011 Wiley Periodicals, Inc.