Vascular aging leads to structural and functional changes. Iliac arteries (IA) provide blood flow to lower urinary tract and pelvic ischemia has been reported as an important factor for bladder remodeling and overactivity. Dysfunction of the nitric oxide (NO)-cyclic guanosine monophosphate pathway (cGMP) is one factor involved in the development of lower urinary tract (LUT) disorders. Therefore, we hypothesized that ageing-associated LUT disorders is a consequence of lower cGMP productions due to an oxidation of soluble guanylate cylase (sGC) that results in local ischemia. In the present study IA from middle-aged and young rats were isolated and the levels of NO, reactive oxygen species (ROS), the gene expression of the enzymes involved in the NO-pathway and concentration-response curves to the soluble guanylate (sGC) stimulator (BAY 41–2272), sGC activator (BAY 58–2667), tadalafil, acetylcholine (ACh) and sodium nitroprusside (SNP) were determined. In IA from middle-aged rats the gene expression for endothelial nitric oxide synthase and the ROS were lower and higher, respectively than the young group. The relaxations induced by ACh and SNP were significantly lower in IA from middle-aged rats. In IA from middle-aged rats the mRNA expression of PDE5 was 55% higher, accompanied by lower relaxation induced by tadalafil. On the other hand, the gene expression for sGCα1 were similar in IA from both groups. Both BAY 41–2272 and BAY 58–2667 produced concentration-dependent relaxations in IA from both groups, however, the latter was 9-times more potent than BAY 41–2272 and produced similar relaxations in IA in both middle-aged and young groups. Yet, the sGC oxidant, ODQ increased the relaxation and the cGMP levels induced by BAY 58–2667. On the other hand, in tissues stimulated with SNP, tadalafil and BAY-2272, the intracellular levels of cGMP were lower in IA from middle-aged than young rats. In conclusion, our results clearly showed that the relaxations induced by the endothelium-dependent and -independent agents, by the PDE5 inhibitor and by sGC stimulator were impaired in IA from aged rats, while that induced by sGC activator was preserved. It suggests that sGC activator may be advantageous in treating ischemia-related functional changes in the lower urinary tract organs in situations where the NO levels are reduced.

血管老化导致结构和功能的变化。髂动脉（IA）为下尿路提供血流，据报道盆腔缺血是膀胱重塑和过度活动的重要因素。一氧化氮 (NO)-环磷酸鸟苷途径 (cGMP) 功能障碍是导致下尿路 (LUT) 疾病发生的因素之一。因此，我们假设与衰老相关的 LUT 疾病是由于可溶性鸟苷酸环化酶 (sGC) 氧化导致局部缺血而导致 cGMP 产量降低的结果。本研究分离了中年和幼龄大鼠的 IA，并测定了 NO、活性氧 (ROS) 的水平、参与 NO 途径的酶的基因表达以及可溶性鸟苷酸 (sGC) 的浓度-反应曲线。 ）测定了刺激剂（BAY 41-2272）、sGC激活剂（BAY 58-2667）、他达拉非、乙酰胆碱（ACh）和硝普钠（SNP）。在中年大鼠的IA中，内皮一氧化氮合酶和ROS的基因表达分别低于和高于年轻组。中年大鼠 IA 中由 ACh 和 SNP 诱导的松弛显着较低。在中年大鼠 IA 中，PDE5 mRNA 表达量高出 55%，同时他达拉非诱导的松弛程度较低。另一方面，两组 IA 中 sGCα1 的基因表达相似。 BAY 41-2272 和 BAY 58-2667 均在两组中产生浓度依赖性的 IA 松弛，然而，后者比 BAY 41-2272 强 9 倍，并且在中年组和青年组中产生相似的 IA 松弛。 。然而，sGC 氧化剂 ODQ 增加了 BAY 58-2667 诱导的松弛和 cGMP 水平。 另一方面，在用SNP、他达拉非和BAY-2272刺激的组织中，中年大鼠IA中的细胞内cGMP水平低于年轻大鼠。总之，我们的结果清楚地表明，在老年大鼠 IA 中，内皮依赖性和非依赖性药物、PDE5 抑制剂和 sGC 刺激剂诱导的舒张受到损害，而 sGC 激活剂诱导的舒张得以保留。这表明，在 NO 水平降低的情况下，sGC 激活剂可能有利于治疗下泌尿道器官的缺血相关功能变化。