Mechanism of vasorelaxation and role of endogenous hydrogen sulfide production in mouse aorta
AIMS Hydrogen sulfide (H(2)S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H(2)S on vascular tone. MAIN METHODS We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H(2)S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues. KEY FINDINGS We have found that in rat aortic rings: (1) H(2)S decreases ATP levels; (2) relaxations to H(2)S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H(2)S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP)-nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of K(ATP) channels is limited, while Cl(-)/HCO(3)(-) channels have a role in the relaxations. (6): We have observed that high concentrations of H(2)S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree. SIGNIFICANCE H(2)S, a new gasotransmitter of emerging importance, leads to relaxation via Cl(-)/HCO(3)(-) channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue.