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.
Adult female Sprague Dawley rats were used.
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-NG-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 μmol/l) instillation. All drugs were delivered intravenously except for L-NAME, which was intravesically administered.
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.
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.