Work

The effect of dehydroepiandrosterone on the vascular system: role of H2S/NO pathways

Year: 2026

Type: article

Abstract: Dehydroepiandrosterone (DHEA) is an adrenal steroid hormone that serves as a precursor to androgens and estrogens and participates in several physiological processes. Its levels naturally decline with age, and reduced DHEA concentrations have been associated with an increased risk of cardiovascular disease. However, this relationship is complex, and further research is required to clarify whether DHEA supplementation may help to prevent age-related vascular dysfunction. Here, we investigated the vascular effects of DHEA using mouse aorta and bovine aortic endothelial cells (BAEC), focusing on the potential involvement of hydrogen sulfide (H 2 S). DHEA exhibited a more pronounced vasorelaxant effect in endothelium intact aortas, mediated not only by nitric oxide (NO) but also by H 2 S. A significant increase in H 2 S production was observed following incubation of the aorta with DHEA compared to the vehicle. In addition to H 2 S, the involvement of L-type calcium channels in DHEA-induced vasorelaxation was found. Nifedipine, an inhibitor of L-type calcium channels, significantly reduced DHEA-induced vasorelaxation, and vice versa , suggesting a shared target. Consistent with the aortic findings, an increase in NO formation was observed in BAEC exposed to DHEA. Using two complementary approaches, we further demonstrate that DHEA enhanced H 2 S production in BAEC, with effects persisting for up to 2 hours. Collectively, these findings suggest that DHEA promotes vasodilation through dual NO- and H 2 S-dependent pathways, along with modulation of L-type calcium channels. Our data provide new insights into the mechanisms of action of DHEA, supporting its protective role in the vasculature. • Hydrogen sulfide, together with nitric oxide, is involved in DHEA-induced relaxation in mouse aorta • DHEA exposure causes an increase in hydrogen sulfide in BAEC • DHEA causes vasorelaxation either in the presence or in the absence of endothelium • DHEA vasorelaxant effect involved K ATP and potassium and L-type calcium channels • DHEA vasorelaxing effect does not involve estrogen and androgen receptors activation.

Source: European Journal of Pharmacology

DOI: 10.1016/j.ejphar.2026.178957