(250) NLRP3 Inflammasome Might Contribute to Erectile Dysfunction Induced by Chronic Unpredictable Stress in Male Mice

Abstract

Abstract Introduction Introduction: The association of stress with erectile dysfunction (ED) is well known, however, it is not clear whether psychological stressors affect the vasculature and the erectile tissue in a manner that could contribute to a vasculogenic erectile dysfunction. Besides hormonal changes, cellular damage induced by stress could lead to the activation of the NLRP3, to increase production of cytokines associated with ED. In this study, we aimed to evaluate the reactivity of the corpus cavernosum and pudendal artery of male mice undergoing chronic unpredictable stress (CUS). Objective Objective: We hypothesize that CUS leads to mitochondrial damage and activates the NLRP3 inflammasome leading to impaired reactivity of the pudendal artery and corpus cavernosum which might cause erectile dysfunction. Methods Methods: Male C57Bl/6 mice were submitted to 28 days of chronic unpredictable stress (CUS). The pudendal artery and corpus cavernosum were removed and mounted in a myograph to evaluate reactivity. Tissues were kept in physiological salt solution at 37°C, constantly aerated with 95%O2/5%CO2 and concentration-response curves to acetylcholine (ACh; 1 nM – 30 uM) and phenylephrine (PE; 1 nM – 30 uM) were obtained. Using non-linear regression, we obtained the maximal response (Emax) and potency (pEC50) of ACh and PE. Expression of NLRP3, pro-caspase1 and caspase1 were measured in arteries by Western blot. Data are expressed as mean ± S.E.M. P<0.05 was considered statistically different. Results Results: CUS led to a significant decrease in the maximal relaxation induced by acetylcholine in the pudendal artery (Non-CUS: 96 ± 3% vs CUS: 84 ± 7%, n=6 and 7, respectively) and in the corpus cavernosum (Non-CUS: 88 ± 4% vs CUS: 75 ± 4%, n=7 each group) as well as an impaired contraction to PE in the corpus cavernosum (non-CUS: 1.72 ± 0.17% vs CUS: 1.07 ± 0.15%, n= 7 each group). In arteries, there were no differences in the expression of NLRP3, however, the ratio of caspase1/pro-caspase-1 was increased in CUS, suggesting that CUS increases the NLRP3 inflammasome pathway. Taken together, our data suggest that CUS led to an activation of the NLRP3 inflammasome pathway, and impaired the relaxation of the pudendal artery and corpus cavernosum by a mechanism that might be associated with decreased nitric oxide bioavailability (endothelium-dependent relaxation), whereas impaired contraction might be associated with desensitization of alpha-adrenergic receptors in response to stress. Conclusions Conclusion: Our findings demonstrate that stress impairs the reactivity of the corpus cavernosum and pudendal artery likely associated with the activation of NLRP3 inflammasome, which might play a role in the development of erectile dysfunction in stressed males. Disclosure No.