环磷酸鸟苷
硝普钠
医学
cGMP特异性磷酸二酯酶5型
一氧化氮
西地那非
排尿
伐地那非
药理学
膀胱测量
内分泌学
膀胱过度活动
一氧化氮合酶
内科学
膀胱
泌尿系统
他达拉非
病理
替代医学
作者
R. Caremel,Stéphanie Oger-Roussel,Delphine Behr‐Roussel,P. Grise,François Giuliano
标识
DOI:10.1016/j.eururo.2010.07.026
摘要
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.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-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.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.
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