title: Inhibitory effects of hyperoxia and methemoglobinemia on H(2)S induced ventilatory stimulation in the rat.
abstract: The aim of this study was to clarify, using in vitro and in vivo approaches in the rat, the site of mediation of the inhibition of H(2)S induced arterial chemoreceptor stimulation, by hyperoxia and methemoglobinemia. We first determined the ventilatory dose-response curves during intravenous injections of H(2)S. A very high dose of NaHS, i.e. 0.4 μmol (concentration: 800 μM), was needed to stimulate breathing within 1s following i.v. injection. Above this level (and up to 2.4 μmol, with a concentration of 4800 μM), a dose-dependent effect of H(2)S injection was observed. NaHS injection into the thoracic aorta produced the same effect, suggesting that within one circulatory time, H(2)S pulmonary exchange does not dramatically reduce H(2)S concentrations in the arterial blood. The ventilatory response to H(2)S was abolished in the presence of MetHb (12.8%) and was significantly depressed in hyperoxia and, surprisingly, in 10% hypoxia. MetHb per se did not affect the ventilatory response to hypoxia or hyperoxia, but dramatically enhanced the oxidation of H(2)S in vitro, with very fast kinetics. These findings suggest that, the decrease/oxidation of exogenous H(2)S in the blood is the primary effect of MetHb in vivo. In contrast, the in vitro oxidative properties of blood for H(2)S were not affected by the level of [Formula: see text] between 23 and >760 mmHg. This suggests that the inhibition of the ventilatory response to H(2)S by hyperoxia during aortic or venous injection originates within the CB and not in the blood. The implications of these results on the role of endogenous H(2)S in the arterial chemoreflex are discussed.
authors.affiliation: Pennsylvania State University, College of Medicine, Division of Pulmonary and Critical Care Medicine, Penn State Hershey Medical Center, 500 University Dr., Hershey, PO Box 850, MC H047, PA 17033-0850, USA.
authors.forename: Andry
authors.initials: A
authors.lastname: Van de Louw
authors.forename: Philippe
authors.initials: P
authors.lastname: Haouzi
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002344:Carotid Body / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000009:adverse effects*; D018496:Hyperoxia / Q000503:physiopathology*; D006985:Hyperventilation / Q000139:chemically induced; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008706:Methemoglobin / Q000502:physiology*; D008708:Methemoglobinemia / Q000139:chemically induced / Q000378:metabolism; D009573:Nitrites; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex; D012119:Respiration / Q000187:drug effects*; D056152:Respiratory Rate / Q000187:drug effects*; D013440:Sulfides / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009573:Nitrites; D013440:Sulfides; D008706:Methemoglobin; D010100:Oxygen; D006862:Hydrogen Sulfide