Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas.
Hydrogen sulfide (H(2)S) has been proposed to mediate hypoxic vasoconstriction (HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H(2)S. Here we examined the relationship between H(2)S and O(2) in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H(2)S (Na(2)S) 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 H(2)S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H(2)S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H(2)S-synthesizing enzyme, cystathionine beta-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine lambda-lyase. Oxygen consumption (M(O(2))) of hagfish DA was constant between 15 and 115 mmHg P(O(2)) (1 mmHg=0.133 kPa), decreased when P(O(2)) <15 mmHg, and increased after P(O(2)) exceeded 115 mmHg. 10 micromol l(-1) H(2)S increased and > or =100 micromol l(-1) H(2)S decreased M(O(2)). Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased M(O(2)). These results show that H(2)S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H(2)S was enhanced at low P(O(2)), it is unlikely that H(2)S contractions are mediated by either H(2)S-NO interaction or an oxidation product of H(2)S. These experiments also provide additional support for the hypothesis that the metabolism of H(2)S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle.
Olson
Kenneth R
KR
Indiana University School of Medicine-South Bend, 1234 Notre Dame Avenue, South Bend, IN 46617, USA. kolson@nd.edu
Forgan
Leonard G
LG
Dombkowski
Ryan A
RA
Forster
Malcolm E
ME
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001158:Arteries / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000139:chemically induced*; D003541:Cystathionine beta-Synthase / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D006196:Hagfishes / Q000502:physiology*; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D019811:Hydroxylamine / Q000494:pharmacology; D007798:Lampreys / Q000502:physiology; D017686:Oncorhynchus mykiss / Q000502:physiology; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*
D002316:Cardiotonic Agents; D019811:Hydroxylamine; D002217:Carbachol; D003541:Cystathionine beta-Synthase; D003545:Cysteine; D010100:Oxygen; D006862:Hydrogen Sulfide