(085) Montelukast, a LRRC8A Inhibitor Decreases the Contractile Response to Phenylephrine in the Corpus Cavernosum of Diabetic Mice

Abstract Introduction Increased reactive oxygen species are often correlated with erectile dysfunction (ED) by enhancing contractility and favoring the flaccid state of penis (which is mainly mediated α-adrenergic innervation) decreasing relaxation corpus cavernosum (CC) associated decreased nitric oxide (NO) bioavailability. Leucine Rich Repeat Containing 8 (LRRC8) Volume Regulated Anion Channels (VRACs) regulates Nox1 modulates extracellular production superoxide anion (O2•-). Downregulation LRRC8 O2•- we have demonstrated improved reduced contraction pudendal artery in LRRC8A knockout mice. Objective In this study, aim to test hypothesis that inhibition Nox or decreases phenylephrine (PE)-induced CC diabetic Methods To hypothesis, (dbdb-/-, 16-week-old) mice were mounted myographs, elicited PE was performed absence repeated presence inhibitor, montelukast Nox1/Nox4 GKT137831. The maximal inhibitor taken as 100%, calculated a percentage attained inhibitor. Results Contraction induced (1.27 + 0.2 mN) similar observed control (1.26 0.4 mN). montelukast, PE-induced significantly reduced, reaching 69 7% 65 10% group, respectively. GKT137831, only group (68 9% contraction), whereas reduction not significant (82 14% contraction). Conclusions This first study demonstrating that, CC, contractile response stimulation may be production, which plays role development ED. Since great number patients benefited phosphodiesterase 5 inhibitors therapy, might potential therapeutic target for new drugs improve sexual function diabetes. Disclosure No