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Pre‐junctional α 2 ‐adrenoceptors modulation of the nitrergic transmission in the pig urinary bladder neck
Author(s) -
Hernández Medardo,
Recio Paz,
Victoria Barahona María,
Bustamante Salvador,
Peña Lidia,
Cristina Martínez Ana,
GarcíaSacristán Albino,
Prieto Dolores,
Orensanz Luis M.
Publication year - 2007
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.20368
Subject(s) - rauwolscine , tetrodotoxin , endocrinology , medicine , guanethidine , neurotransmission , nitric oxide , cholinergic , nitric oxide synthase , stimulation , phenylephrine , urinary bladder , agonist , antagonist , receptor , prazosin , blood pressure
Aims To investigate the nitric oxide (NO)‐mediated nerve relaxation and its possible modulation by pre‐junctional α 2 ‐adrenoceptors in the pig urinary bladder neck. Methods Urothelium‐denuded bladder neck strips were dissected, and mounted in isolated organ baths containing a physiological saline solution (PSS) at 37°C and continuously gassed with 5% CO 2 and 95% O 2 , for isometric force recording. The relaxations to transmural nerve stimulation (electrical field stimulation [EFS]) or exogenously applied NO were carried out on strips pre‐contracted with 1 µM phenylephrine (PhE) and treated with guanethidine (10 µM) and atropine (0.1 µM), to block noradrenergic neurotransmission and muscarinic receptors, respectively. Results EFS (0.2–1 Hz, 1 msec duration, 20 sec trains, current output adjusted to 75 mA) evoked frequency‐dependent relaxations which were abolished by the neuronal voltage‐activated Na + channel blocker tetrodotoxin (TTX, 1 µM). These responses were potently reduced by the nitric oxide synthase (NOS) inhibitor N G ‐nitro‐ L ‐arginine (L‐NOARG, 30 µM) and further reversed by the NO synthesis substrate L ‐arginine (L‐ARG, 3 mM). The α 2 ‐adrenoceptor agonist BHT‐920 (2 µM) reduced the electrically evoked relaxations, its effectiveness being higher on the responses induced by low frequency stimulation. BHT‐920‐elicited reductions were fully reversed by the α 2 ‐adrenoceptor antagonist rauwolscine (RAW, 1 µM). Exogenous NO (1 µM–1 mM) induced concentration‐dependent relaxations which were not modified by BHT‐920, thus eliminating a possible post‐junctional modulation. Conclusions These results indicate that NO is involved in the non‐adrenergic non‐cholinergic (NANC) inhibitory neurotransmission in the pig urinary bladder neck, the release of NO from intramural nerves being modulated by pre‐junctional α 2 ‐adrenoceptor stimulation. Neurourol. Urodynam. 26:578–583, 2007. © 2007 Wiley‐Liss, Inc.