Divergent Molecular Mechanisms Underlay CO- and CORM-2-Induced Relaxation of Corpora Cavernosa

摘要

Introduction. 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. Aim. 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. Methods. Organ bath studies were performed measuring isometric tension on isolated mice corpora cavernosa (CC) strips. Responses to CO (10-300μmol/L) and CORM-2 (10-100μmol/L) were measured in the presence/absence of activators/inhibitors of different molecular pathways. Main Outcome Measures. CO and CORM-2 relax corporal strips concentration dependently, although the molecular mechanisms behind the corporal relaxation seem to differ completely. Results. 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. Conclusions. 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.