Functional evidence of nitrergic neurotransmission in the human urinary bladder neck.
Nitric oxide (NO) is involved in the non-adrenergic non-cholinergic (NANC) inhibitory neurotransmission of the lower urinary tract. However, functional evidence of this involvement in the human urinary bladder neck has not been consistently demonstrated. Therefore, the current study investigates the relaxations to endogenously released and/or exogenously added NO, in the human bladder neck. 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% CO(2) and 95% O(2), for isometric force recording. The relaxations to transmural nerve stimulation (EFS) or to exogenously applied NO, as an acidified solution of NaNO(2) were carried out on strips precontracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively. EFS (0.5-16Hz) and exogenous NaNO(2) (1muM to 1mM) evoked frequency- and concentration-dependent relaxations, respectively. The nerve responses were abolished by the blockade of neuronal voltage-activated Na(+) channels with tetrodotoxin, indicating their neurogenic character. N(G)-nitro-l-arginine (l-NOARG), a NO synthase inhibitor, abolished the relaxations to nerve stimulation, which were partially reversed by the substrate of NO synthesis l-arginine. l-NOARG failed to modify the relaxations to exogenous NaNO(2). These results suggest that NO is the major NANC inhibitory neurotransmitter in the human urinary bladder neck. Blockers of NO synthase could be useful in therapy for the urinary incontinence produced by intrinsic sphincteric deficiency.
Bustamante
Salvador
S
Departamento de Urología, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain.
Orensanz
Luis M
LM
Recio
Paz
P
Carballido
Joaquín
J
García-Sacristán
Albino
A
Prieto
Dolores
D
Hernández
Medardo
M
D018663:Adrenergic Agents / Q000494:pharmacology; D000328:Adult; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology; D009435:Synaptic Transmission; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D018727:Muscarinic Antagonists; D026941:Sodium Channel Blockers; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; D019001:Nitric Oxide Synthase; D012977:Sodium Nitrite; D006145:Guanethidine