The adrenergic, cholinergic and NANC nerve-mediated contractions of the female rabbit bladder neck and proximal, medial and distal urethra

Abstract

1. The nerve-mediated contraction of the female rabbit bladder neck and different portions of the urethra (proximal, medial and distal) was studied in vitro by electrical stimulation (50 V, 30 Hz, 0.05 ms width, trains of 5 s every 5 min) by use of a superfusion system. 2. The amplitude (E(max)) and the duration (D(max)) of the stimulated contraction were studied in the four tissues. The E(max) value was significantly higher in distal urethra (2.07 ± 0.15 g) compared to the bladder neck (1.08 ± 0.10 g), proximal urethra (0.73 ± 0.07 g) and medial urethra (0.87 ± 0.07 g). In contrast, the D(max) value appeared slightly but significantly lower (P < 0.05) in distal urethra (68.5 ± 2.3 s) than in bladder neck (76.7 ± 6.0 s), proximal urethra (54.5 ± 5.0 s) and medial urethra (81.3 ± 3.5 s). 3. Cocaine (1 μM) significantly increased the basal E(max) value in proximal, medial and distal urethra and the basal D(max) values in the four tissues. 4. Prazosin (1 μM) significantly reduced E(max) value in proximal, medial and distal urethra and D(max) value in bladder neck and proximal urethra. Atropine (1 μM) also significantly reduced E(max) values in bladder neck and proximal urethra and reduced D(max) value in bladder neck, but not in other tissues. Yohimbine (0.1 μM) was devoid of effect in the four tissues. 5. The association of prazosin (1 μM) and atropine (1 μM) did not modify the E(max) and the D(max) values of the electrically-induced contractions, except in proximal urethra and in bladder neck where an additive inhibitory effect (on E(max) only) was observed compared to prazosin and atropine alone. 6. The residual contractile response after combined treatment with prazosin and atropine was significantly diminished by tetrodotoxin (TTX; 1 μM) but not completely abolished. These NANC contractions were insensitive to P2X-purinoceptor desensitization by continuous tissue perfusion with α,β-methylene ATP (30 μM). 7. These results demonstrate that bladder neck and proximal urethra are mainly innervated by the parasympathetic nervous system, whereas medial and distal urethras are to a greater extent under the control of the sympathetic innervation. The residual responses, insensitive to prazosin and atropine, may indicate a NANC innervation in the four tissues. However, the nature of the NANC neurotransmitter remains to be identified.