Serum from Men with the Severe Form of COVID-19 Impairs the Nitric Oxide Signaling Pathway in Isolated Corpus Cavernosum from Mice: An In Vitro Study

Abstract

Introduction. Erectile dysfunction (ED) is characterized by the inability to achieve and/or maintain an erection during sexual activity. Vascular-related diseases such as obesity, diabetes, aging, and hypertension are known risk factors that increase the prevalence of ED. The viral infection caused by SARS-CoV-2, the etiological agent of COVID-19, can evolve into mild to severe forms. Patients with comorbidities such as diabetes and obesity present a more severe state of the disease. The cytokine storm and reactive oxygen species associated with COVID-19 can lead to progressive systemic inflammation and vascular dysfunction. This study is aimed at assessing the in vitro effects of serum obtained from unvaccinated men who had the severe form of COVID-19 in isolated corpus cavernosum (CC) from healthy mice. Methods. Concentration-response curves to endothelium-dependent and endothelium-independent substances were carried out in isolated CC from mice after being incubated (3 hours) with serum obtained from patients with and without (control group) the severe form of COVID-19. qRT-PCR and western blotting were also carried out. Results. The relaxing responses induced by acetylcholine (ACh), a nitric oxide donor (sodium nitroprusside), soluble guanylate cyclase (sGC) stimulator (BAY 63-2521), and phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) were significantly reduced in CC incubated with COVID-19 serum when compared with CC incubated with the control serum. Nonetheless, the relaxation induced by the sGC activator BAY 58-2667 was unaffected in CC stimulated with the COVID-19 serum. The coincubation of control or COVID-19 serum with a free radical scavenger (PEG-SOD; 150 UI/mL, 3 hours) significantly improved the relaxation induced by ACh. On the other hand, catalase did not improve ACh-induced relaxation in CC incubated with the sera. The gene expression for PDE5 and NADPH oxidase type 4 was increased in CC stimulated with COVID-19 serum in comparison to tissues stimulated with the control serum. The protein expression for sGC subunits was similar in both groups. Conclusion. Serum obtained from unvaccinated men who presented the severe form of COVID-19 impaired the relaxation induced by cyclic guanosine monophosphate-accumulating substances in CC from mice.