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 (H(2)S) is involved in transducing these effects in mammals. The rationale for this hypothesis is twofold. Firstly, inhalation of a 20-80 ppm H(2)S reduces metabolism in small mammals and this effect is analogous to that of hypoxia. Secondly, endogenous H(2)S 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 H(2)S and to 10% O(2) in small and large rodents (20g mice and 700g rats) wherein the metabolic response to hypoxia has been shown to differ according to body mass. H(2)S and hypoxia produced profound depression in metabolic rate in the mice, but not in the large rats. The depression was much faster with H(2)S than with hypoxia. The relative hyperventilation produced by hypoxia in the mice was replaced by a depression with H(2)S, which paralleled the drop in metabolic rate. In the larger rats, ventilation was stimulated in hypoxia, with no change in metabolism, while H(2)S affected neither breathing nor metabolism. When mice were simultaneously exposed to H(2)S and hypoxia, the stimulatory effects of hypoxia on breathing were abolished, and a much larger respiratory and metabolic depression was observed than with H(2)S alone. H(2)S had, therefore, no stimulatory effect on the arterial chemoreflex. The ventilatory depression during hypoxia and H(2)S in small mammals appears to be dependent upon the ability to decrease metabolism.
Haouzi
Philippe
P
Pennsylvania State University, College of Medicine, Heart and Vascular Institute, 500 University Drive, Hershey, PA 17033, USA. phaouzi@hmc.psu.edu
Bell
Harold J
HJ
Notet
Veronique
V
Bihain
Bernard
B
D000465:Algorithms; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D005246:Feedback / Q000502:physiology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects*
D002245:Carbon Dioxide; D006862:Hydrogen Sulfide