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 °C and continuously gassed with 5% CO2 and 95% O2, for isometric force recording. The relaxations to transmural nerve stimulation (EFS) or to exogenously applied NO, as an acidified solution of NaNO2 were carried out on strips precontracted with phenylephrine, and treated with guanethidine and atropine, to block noradrenergic neurotransmission and muscarinic receptors, respectively. EFS (0.5–16 Hz) and exogenous NaNO2 (1 μM to 1 mM) 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. NG-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 NaNO2. 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.