Functional study of the bladder mechanosensitive afferent pathways

我们建立了在体大鼠膀胱机械敏感初级传入神经纤维单位传入活动(SaaS)的测量方法，并在本实验装置中观察了几种药物对这些SaaS的影响。结果表明，NO底物L精氨酸、β3肾上腺素能受体(β3 AR)激动剂他达拉非和西地那非以及米雷贝格隆均能抑制Aδ和C机械敏感型传入纤维。此外，膀胱中TRPV4的激活，可能是尿路上皮细胞，通过P2X-嘌呤受体介导的机械敏感的辣椒素不敏感的C纤维的激活，促进了排尿反射。此外，L-精氨酸和他达拉非均能抑制环磷酰胺的代谢物丙烯醛所引起的双纤维激活。我们进一步研究了SaaS和膀胱微收缩之间的关系，这已经被认为是肌源性起源的。结果表明，米拉贝隆对膀胱微收缩和Aδ纤维传入活动均有抑制作用，提示这种微收缩可能与Aδ纤维的机械敏感性传入活动有关。在另一项研究中，我们建立了SaaS与节律性膀胱收缩同步的测量方法。我们发现，大鼠膀胱A、δ和C纤维的机械敏感型传入活动都能对拉伸和收缩刺激作出反应。L-精氨酸和米雷贝隆抑制膀胱收缩引起的机械敏感传入神经的兴奋。

We have established the measurement of single-unit afferent activities (SAAs) of the bladder mechanosensitive primary afferent nerve fibers in in vivo rats, and have investigated the effect of several drugs on these SAAs in this experimental set-up. The study demonstrated that L-arginine (an NO substrate), tadalafil and sildenafil (PDE5 inhibitors), and mirabegron (a β3-adrenoceptor (β3-AR) agonist), can inhibit both Aδ- and C- mechanosensitive afferent fiberst. Moreover, the activation of TRPV4 in the bladder, probably urothelium, facilitated the micturition reflex by P2X-purinoceptor-mediated activation of the mechanosensitive capsaicin-insensitive C-fibers. In addition, L-arginine and tadalafil can inhibit the activation of both fibers induced by intravesical acrolein, a metabolite of cyclophosphamide. We further investigated the relationship between the SAAs and bladder microcontractions, which have been recognized of myogenic origin. The results showed that mirabegron inhibited both bladder microcontractions and Aδ-fiber afferent activity, suggesting that the microcontractions may be linked to the mechanosensitive afferent activities of Aδ-fibers. In another study, we have established the measurement of SAAs synchronized with rhythmic bladder contractions. We found that mechanosensitive afferent activities of both Aδ- and C- fibers of the rat bladder are capable of being responsive to both stretch and contractile stimuli, and. that L-arginine and mirabegron inhibit the activation of mechanosensitive afferent nerves induced by bladder contractions.