Iselin C E, Ny L, Larsson B, Schaad N C, Alm P, Graber P, Morel D R, Andersson K E
Department of Surgery, Geneva University Hospital, Switzerland.
Eur Urol. 1998;33(2):214-21. doi: 10.1159/000019539.
To investigate the nitric oxide synthase (NOS)/nitric oxide (NO) and heme oxygenase (HO)/carbon monoxide (CO) pathways in the human isolated ureter.
Immunohistochemical studies were performed. NOS activity was measured by monitoring the conversion of [3H]-arginine to [3H]-citrulline. Functional inhibitory effects mediated by NO and CO were assessed, and correlated with cyclic nucleotide levels.
The overall innervation of the ureter was moderate, however more prominent in the distal segment. Relative to overall innervation, neuronal NOS-immunoreactive (-IR) nerves were few. In the submucosa, neuronal NOS-IR varicose nerves were found closely together with varicose nerves containing calcitonin gene-related peptide immunoreactivity. In the distal ureter, nerve trunks were demonstrated, expressing immunoreactivity for HO-2. Ca(2+)-dependent NOS activity was 53 +/- 13 pM/mg protein/h. In isolated preparations, NO decreased endothelin-1-induced contraction in a concentration-dependent manner. In strips exposed to NO, there was a 6-fold increase of the cyclic GMP levels in comparison to control preparations (p < 0.001). CO exerted no effect on induced ureteral tone.
Neuronal NOS- and HO-2-IR nerves can be demonstrated in the human ureter, where NO, but probably not CO, may contribute to the regulation of tone. Although the physiological roles for NO and CO remain to be established, the NOS/NO/cyclic GMP pathway may be a target for drugs producing relaxation of the human ureter. The richer innervation of the distal ureter may be of importance for the coordination of ureteral peristalsis and the motility of the ureterovesical junction.
研究人离体输尿管中的一氧化氮合酶（NOS）/一氧化氮（NO）和血红素加氧酶（HO）/一氧化碳（CO）通路。
进行免疫组织化学研究。通过监测[3H]-精氨酸向[3H]-瓜氨酸的转化来测定NOS活性。评估由NO和CO介导的功能抑制作用，并与环核苷酸水平相关联。
输尿管的总体神经支配适中，但在远端段更为明显。相对于总体神经支配，神经元型一氧化氮合酶免疫反应性（-IR）神经较少。在黏膜下层，发现神经元型一氧化氮合酶免疫反应性曲张神经与含有降钙素基因相关肽免疫反应性的曲张神经紧密相邻。在输尿管远端，显示出神经干，表达HO-2的免疫反应性。钙依赖性NOS活性为53±13 pM/mg蛋白/小时。在离体标本中，NO以浓度依赖性方式降低内皮素-1诱导的收缩。与对照标本相比，暴露于NO的条带中环鸟苷酸水平增加了6倍（p<0.001）。CO对诱导的输尿管张力无影响。
在人输尿管中可证实存在神经元型一氧化氮合酶和HO-2免疫反应性神经，其中NO可能参与输尿管张力的调节，而CO可能不参与。尽管NO和CO的生理作用仍有待确定，但NOS/NO/环鸟苷酸通路可能是产生人输尿管松弛的药物的作用靶点。输尿管远端更丰富的神经支配可能对输尿管蠕动和输尿管膀胱连接部的运动协调具有重要意义。
