Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Kiss
Levente
L
Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, NJ 07103-2714, USA.
Deitch
Edwin A
EA
Szabó
Csaba
C
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D001013:Aorta, Thoracic / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D054086:KATP Channels / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010085:Oxidative Phosphorylation; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D054086:KATP Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005905:Glyburide; D006862:Hydrogen Sulfide
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