Akademik Veri Yönetim Sistemi
European Journal of Pharmacology, cilt.997, 2025 (SCI-Expanded)
Background: Phosphodiesterase type-5 inhibitors, first-line treatments for erectile dysfunction (ED), are insufficient in 30–40 % of patients, highlighting an unmet therapeutic need. Hydrogen sulfide (H2S) compensates for NO deficiency and improves erectile function. We hypothesized that H2S contributes to the smooth muscle relaxation in penile arteries and erectile tissue induced by osthole. Methods: We investigated the effects of osthole on H2S-producing enzyme expression and H2S production in murine erectile tissues by Western blot and H2S microsensor experiments. To evaluate the role of H2S in osthole-induced relaxations, myography was conducted on mouse corpus cavernosum (MCC) and rat pudendal artery (RPA). While monitoring vascular responses, endogenous H2S production was simultaneously measured by an H2S microsensor inserted in the RPA lumen. Intracavernosal pressure was measured in anesthetized rats to evaluate the effect of osthole on erectile function. Results: Osthole induced relaxation by increasing H2S synthesis and enhancing the expression of H2S-producing enzymes, as well as promoting H2S formation in murine erectile tissues. Osthole relaxed RPA while simultaneously increasing H2S levels in the arterial lumen. Osthole also amplified L-cysteine- and Na2S-induced relaxations and increased luminal H2S levels. Additionally, osthole increased endothelium-dependent and independent relaxations by inducing H2S synthesis. Osthole improved erection by facilitating erectile responses in rats. Conclusion: Our novel approach, based on simultaneous measurements of endogenous H2S production in the arterial lumen and vascular contractility, suggests that H2S contributes to osthole-induced relaxation of penile tissue, proposing that osthole may be a promising drug candidate for treating ED, particularly when caused by endothelial dysfunction.