The possible role of hydrogen sulfide as a smooth muscle cell proliferation inhibitor in rat cultured cells

Abstract

Hydrogen sulfide (H₂S) was recently suggested to be a possible endogenous gasotransmitter in physiological concentration. For the purpose of understanding its possible role in the regulation of the cardiovascular system, we explored the potential effect of H₂S on the proliferation of cultured aortic vascular smooth muscle cells (VSMCs) of rats and mitrogen-activated protein kinase (MAPK) as a signaling transduction pathway. Vascular smooth muscle cells were cultured in vitro and the cells were divided into six groups: (1) control group, (2) serum group, (3) endothelin group, (4) NaHS group, (5) serum + NaHS group, and (6) endothelin + NaHS group. VSMC proliferation was measured by [³H]thymidine ([³H]TdR) incorporation and MAPK activity in the VSMCs was determined by radioactivity assay. The results showed that endothelin-1 increased VSMC [³H]TdR incorporation 2.39-fold (P ≪ 0.01) and MAPK activity 1.62-fold (P ≪ 0.01), as compared with controls. Hydrogen sulfide at 5 × 10⁻⁵ mol/l, 1 × 10⁻⁴ mol/l, and 5 × 10⁻⁴ mol/l decreased VSMC [³H]TdR incorporation by 16.8%, 26.60%, and 37.40%, respectively, and reduced MAPK activity by 7.37% (P ≫ 0.05), 23.39%, and 33.57%, respectively (P ≪ 0.01). The results demonstrated that H₂S could dose-dependently suppress the proliferation of VSMCs through the MAPK pathway.