Comparison of the metabolic and ventilatory response to hypoxia and H₂S in unsedated mice and rats

Hypoxia alters the control of breathing and metabolism by increasing ventilation through the arterial chemoreflex, an effect which, in small-sized animals, is offset by a centrally mediated reduction in metabolism and respiration. We tested the hypothesis that hydrogen sulfide (H₂S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. Firstly, inhalation of a 20-80 ppm H₂S reduces metabolism in small mammals and this effect is analogous to that of hypoxia. Secondly, endogenous H₂S appears to mediate some of the cardio-vascular effects of hypoxia in non-mammalian species. We, therefore, compared the ventilatory and metabolic effects of exposure to 60 ppm H₂S and to 10% O₂ in small and large rodents (20 g mice and 700 g rats) wherein the metabolic response to hypoxia has been shown to differ according to body mass. H₂S and hypoxia produced profound depression in metabolic rate in the mice, but not in the large rats. The depression was much faster with H₂S than with hypoxia. The relative hyperventilation produced by hypoxia in the mice was replaced by a depression with H₂S, which paralleled the drop in metabolic rate. In the larger rats, ventilation was stimulated in hypoxia, with no change in metabolism, while H₂S affected neither breathing nor metabolism. When mice were simultaneously exposed to H₂S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H₂S alone. H₂S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H₂S in small mammals appears to be dependent upon the ability to decrease metabolism.