The involvement of H2S/NO pathways in the DHEA induced relaxation

Abstract

Dehydroepiandrosterone (DHEA) is a precursor of androgen and estrogen hormones, and it is synthesized in the adrenal cortex. His levels have an age-dependent decline and low levels of DHEA were associated with cardiovascular disease. DHEA causes nitric oxide (NO) release in bovine aortic endothelial cells (BAEC) independently from estrogen and androgen receptors. Hydrogen sulfide (H2S) is the other important gasotransmitter in vascular homeostasis. Little is known about the mechanism of action driven by DHEA at the vascular level. In particular, the involvement of H2S/NO pathways in the DHEA induced relaxation has been investigated. Functional studies on CD1 mice aorta were used to perform a cumulative concentration curve of DHEA on a stable tone of phenylephrine. To investigate the mechanism(s) of action we used inhibitors of the androgen receptor, of the enzyme synthesis NO and H2S, and a blocker of KATP channel (target of H2S). Furthermore, we incubated the aorta with DHEA to measure H2S level. Finally, we treated BAEC with DHEA to measure H2S and NO levels at different times of incubation. We found that the relaxation induced by DHEA was partially dependent on the endothelium and this effect was mediated by either H2S and NO. Moreover, the relaxation did not involve the androgen receptor. Finally, the stimulation of H2S production by DHEA was fast both in aorta and in BAEC ( Fig. 1 ). These data bring new information on the mechanism(s) of action of DHEA in the vasculature and supports its protective role not only through NO but also through H2S synthesis.