Relaxant effect of menthol on the pudendal artery and corpus cavernosum of lean and db/db mice: A refreshing approach to diabetes-associated erectile dysfunction.

Abstract: Erectile dysfunction is one of the most underestimated complications of diabetes. Menthol, known for its cooling sensation, is commonly featured in products that claim to enhance sexual performance, yet its effects on penile vasculature lack scientific validation. This study aimed to evaluate whether menthol induces relaxation in the corpus cavernosum and pudendal arteries isolated from diabetic mice. Male lean and db/db mice (20-24 weeks old) were used. Assessments included murinometric data, histology, confocal microscopy to evaluate arterial structure, DHE staining for reactive oxygen species (ROS), immunofluorescence, and Western blotting for TRPM8 expression. The isometric force was measured on a wire myograph (pudendal artery) or organ bath (corpus cavernosum). Our results demonstrated that menthol induced a similar relaxation in pudendal arteries from db/db and lean, although it had a reduced effect in the corpus cavernosum from db/db. The db/db exhibited distinct structural and functional phenotypes characterized by increased fibrosis, ROS levels in the corpus cavernosum, and reduced relaxation to acetylcholine and sildenafil in pudendal arteries. TRPM8 was expressed but it seems not to be the exclusive target for menthol-induced relaxation in the corpus cavernosum of lean mice and in the pudendal arteries of both groups. Furthermore, menthol pre-exposure decreased the efficacy of phenylephrine in pudendal arteries from both groups and in the corpus cavernosum of lean mice, without affecting the potency or efficacy of acetylcholine. These findings suggest that menthol-induced relaxation and reduction of phenylephrine efficacy may hold promise for decreasing penile vascular resistance and enhancing blood flow to the penis.