Nitric oxide/cyclic guanosine monophosphate signalling mediates an inhibitory action on sensory pathways of the micturition reflex in the rat.
BACKGROUND
Overactive bladder can be associated with a hyperexcitability of bladder afferent C-fibres. Several studies have suggested that nitric oxide (NO) or its downstream signalling could modulate the micturition reflex (MR) by reducing the excitability of bladder afferents.


OBJECTIVE
To evaluate the role of the NO/cyclic guanosine monophosphate (cGMP) signalling pathway on the MR in a model of bladder hyperactivity (BHA) associated with C-fibre activation in the rat.


METHODS
Adult female Sprague Dawley rats were used.


METHODS
Cystometry was performed in anaesthetised rats. The effects of 0.1 mg/kg of sodium nitroprusside (SNP), an NO donor; 10 mg/kg of 8Br-cGMP, a cGMP analogue; 3 mg/kg of sildenafil and 1 mg/kg of vardenafil, two phosphodiesterase type 5 inhibitors (PDE5-I); 10 mg/ml of L-N(G)-nitroarginine methyl ester (L-NAME), an NO synthase inhibitor; and 1 mg/kg of LY-83583, a guanylate cyclase inhibitor, were investigated on BHA during intravesical capsaicin (30 micromol/l) instillation. All drugs were delivered intravenously except for L-NAME, which was intravesically administered.


CONCLUSIONS
SNP, 8Br-cGMP, and PDE5-I increased the intercontraction interval (ICI), while SNP and PDE5-I increased the micturition pressure threshold (MPT). L-NAME and LY-83583 decreased MPT, and L-NAME decreased ICI. 8Br-cGMP decreased the maximum intravesical pressure (MP), contrary to L-NAME and LY-83583. SNP and PDE5-I had no effect on MP. SNP increased the voided volume (VV). PDE5-I and 8Br-cGMP also increased VV, although not significantly. In contrast, L-NAME tended to decrease VV. Although 8Br-cGMP decreased the baseline intravesical pressure, LY-83583 increased it. Neither SNP nor PDE5-I nor L-NAME had any effect on baseline pressure.


CONCLUSIONS
Compounds activating the NO/cGMP pathway inhibited BHA, whereas compounds inhibiting the NO/cGMP pathway increased it. These results indicate that the NO/cGMP signalling pathway is involved in the regulation of the MR, with an action that seems more predominant on the sensory rather on the motor component of the MR in a rat model of BHA associated with C-fibre afferent activation.
Caremel
Romain
R
Charles Nicolle Hospital, Department of Urology, Rouen, France.
Oger-Roussel
Stephanie
S
Behr-Roussel
Delphine
D
Grise
Philippe
P
Giuliano
François A
FA
D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*; D012677:Sensation / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014554:Urination / Q000502:physiology*
D009569:Nitric Oxide; D006152:Cyclic GMP