Department of Pharmacology, Ghent University, Ghent, Belgium.
J Sex Med. 2012 Sep;9(9):2284-92. doi: 10.1111/j.1743-6109.2012.02831.x. Epub 2012 Jul 3.
Similar to nitric oxide (NO), the principal mediator of penile erection, carbon monoxide (CO) possesses vasodilator capacities. However, whether CO could be a therapeutic target for treating erectile dysfunction (ED) is unexplored. The danger associated with systemic administration of CO has led to the development of CO-releasing molecules (CORMs), releasing CO in a local, safe and controlled way. These CORMs have shown positive outcomes in cardiovascular studies. More knowledge on the (patho)physiological functions of CO in erectile function and the potential therapeutic role of CORMs is required.
The present study aims the assessment of the effect of CO and CO donor CORM-2 on the corporal tension and the underlying molecular mechanisms.
Organ bath studies were performed measuring isometric tension on isolated mice corpora cavernosa (CC) strips. Responses to CO (10-300 µmol/L) and CORM-2 (10-100 µmol/L) were measured in the presence/absence of activators/inhibitors of different molecular pathways.
CO and CORM-2 relax corporal strips concentration dependently, although the molecular mechanisms behind the corporal relaxation seem to differ completely.
CO induces corporal relaxation by activating soluble guanylyl cyclase (sGC), increasing cyclic guanosine monophosphate (cGMP) concentrations. The molecular mechanism involved in CORM-2-induced corporal relaxation is not related to sGC activation and remains obscure.
Both CO and CORM-2 induce corporal relaxation, although the underlying molecular mechanisms show no resemblance. That CO induces corporal relaxation through a mechanism similar to that of NO could be of importance as it indirectly offers the possibility that endogenous CO might serve as a backup system for insufficient NO availability in cases of ED. Whether CORM-2 possesses the same capacity remains questionable and requires further research.
类似于一氧化氮（NO），阴茎勃起的主要介质，一氧化碳（CO）具有血管扩张能力。然而，CO 是否可以成为治疗勃起功能障碍（ED）的治疗靶点尚未得到探索。由于 CO 的全身给药存在危险，因此开发了一氧化碳释放分子（CORM），以局部、安全和可控的方式释放 CO。这些 CORM 在心血管研究中显示出了积极的结果。需要更多地了解 CO 在勃起功能中的（病理）生理学功能以及 CORM 的潜在治疗作用。
本研究旨在评估 CO 和 CO 供体 CORM-2 对 corpora 张力的影响及其潜在的分子机制。
通过在离体小鼠海绵体（CC）条上进行等长张力测量，进行器官浴研究。在不同分子途径的激活剂/抑制剂存在/不存在的情况下，测量 CO（10-300 µmol/L）和 CORM-2（10-100 µmol/L）的反应。
CO 和 CORM-2 浓度依赖性地使 corpora 条带松弛，尽管 corpora 松弛背后的分子机制似乎完全不同。
CO 通过激活可溶性鸟苷酸环化酶（sGC）诱导 corpora 松弛，增加环鸟苷酸（cGMP）浓度。CORM-2 诱导 corpora 松弛的分子机制与 sGC 激活无关，目前尚不清楚。
CO 和 CORM-2 均诱导 corpora 松弛，尽管潜在的分子机制没有相似之处。CO 通过类似于 NO 的机制诱导 corpora 松弛可能很重要，因为它间接提供了一种可能性，即内源性 CO 可能作为 ED 情况下 NO 供应不足的后备系统。CORM-2 是否具有相同的能力仍存在疑问，需要进一步研究。
