Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas

Hydrogen sulfide ( H2S) has been proposed to mediate hypoxic vasoconstriction ( HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H2S. Here we examined the relationship between H2S and O-2 in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H2S ( Na2S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries (EBA) but did not affect ventral aortas or afferent branchial arteries; effects similar to those produced by hypoxia. Sensitivity of H2S- mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H2S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H2S- synthesizing enzyme, cystathionine beta-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine.- lyase. Oxygen consumption ((M) over dot (O2)) of hagfish DA was constant between 15 and 115 mmHg P O2 (1mmHg= 0.133 kPa), decreased when P-O2 < 15 mmHg, and increased after P-O2 exceeded 115 mu mmHg. 10 mu mol l(-1) H2S increased and >= 100 mu mol l(-1) H2S decreased (M) over dot (O2). Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased (M) over dot (O2). These results show that H2S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H2S was enhanced at low P-O2, it is unlikely that H2S contractions are mediated by either H2S-NO interaction or an oxidation product of H2S. These experiments also provide additional support for the hypothesis that the metabolism of H2S is involved in oxygen sensing/ signal transduction in vertebrate vascular smooth muscle.