Pre-junctional alpha2-adrenoceptors modulation of the nitrergic transmission in the pig urinary bladder neck.
OBJECTIVE
To investigate the nitric oxide (NO)-mediated nerve relaxation and its possible modulation by pre-junctional alpha2-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 degrees C and continuously gassed with 5% CO2 and 95% O2, 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 microM phenylephrine (PhE) and treated with guanethidine (10 microM) and atropine (0.1 microM), 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 microM). These responses were potently reduced by the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG, 30 microM) and further reversed by the NO synthesis substrate L-arginine (L-ARG, 3 mM). The alpha2-adrenoceptor agonist BHT-920 (2 microM) 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 alpha2-adrenoceptor antagonist rauwolscine (RAW, 1 microM). Exogenous NO (1 microM-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 alpha2-adrenoceptor stimulation.
Hernández
Medardo
M
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Recio
Paz
P
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Victoria Barahona
María
M
Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Bustamante
Salvador
S
Servicio de Urología, Clínica Puerta de Hierro de Madrid, Madrid, Spain.
Peña
Lidia
L
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Cristina Martínez
Ana
A
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
García-Sacristán
Albino
A
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Prieto
Dolores
D
Departamento de Fisiología (Fisiología Animal), Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Orensanz
Luis M
LM
Departamento de Investigación, Hospital Universitario Ramón y Cajal, Madrid, Spain.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013552:Swine; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D019335:Nitroarginine; D015016:Yohimbine; D009569:Nitric Oxide; D013779:Tetrodotoxin; C024763:talipexole; D001120:Arginine; D052248:Nitric Oxide Synthase Type I