Chronic unpredictable stress impairs corpus cavernosum reactivity in mice

Abstract Introduction Stress is associated with erectile dysfunction (ED), 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. A positive correlation between hyperprolactinemia, stress and erectile dysfunction has been demonstrated, and interestingly, prolactin was shown to decrease endothelium nitric oxide and endothelium- dependent vasorelaxation in different vascular beds. In this study, we aimed to evaluate the relaxation of the corpus cavernosum of male and pudendal artery of male and female mice undergoing chronic unpredictable stress (CUS). Objective We aimed to test the hypothesis that vascular impairment caused by CUS leads to impaired relaxation of the pudendal artery and corpus cavernosum which may cause erectile dysfunction. Methods Male and female 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. Data are expressed as mean ± S.E.M. P<0.05 was considered statistically different. Results In the pudendal artery, neither the potency nor the maximal response to ACh was changed by the stress. Contraction to PE was higher in males, compared to females, and there was a trend to be further increased in stressed males. On the other hand, in the corpus cavernosum of stressed males there was a significant decrease in the maximal relaxation induced by acetylcholine (control: 88 ± 4% vs stress: 75 ± 4%, n=7 each group) as well as impaired contraction to PE (control: 1.72 ± 0.17% vs stress: 1.07 ± 0.15%, n= 7 each group). The impaired relaxation might be associated with impaired nitric oxide availability, whereas impaired contraction can be associated with a desensitization of alpha-adrenergic receptors in response to stress. Conclusions Our findings demonstrate that stress impairs the reactivity of the corpus cavernosum, which may contribute to the development of erectile dysfunction in stressed males. Disclosure No