Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas

Abstract

SUMMARY 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 O2 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 β-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine λ-lyase. Oxygen consumption(ṀO2) of hagfish DA was constant between 15 and 115 mmHg PO2 (1 mmHg=0.133 kPa), decreased when PO2 <15 mmHg, and increased after PO2 exceeded 115 mmHg. 10 μmol l–1 H2S increased and ⩾100μmol l–1 H2S decreased ṀO2. Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased ṀO2. 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 PO2, 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.