title: Central heme oxygenase-carbon monoxide pathway in the control of breathing under normoxia and hypoxia.
abstract: Endogenously carbon monoxide (CO) arises from the catabolism of heme to biliverdin, free iron and CO, a process catalyzed by the enzyme heme oxygenase (HO). In the present study, we tested the hypothesis that the central HO-CO pathway plays a role in hypoxia-induced hyperventilation. To this end, we used intracerebroventricular (i.c.v.) injections of the HO inhibitor zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG; 200 nmol) and of heme-lysinate (152 nmol), which is known to induce the HO pathway, and measured respiratory frequency (f), tidal volume (VT) and pulmonary ventilation (VE) by body plethysmograph in conscious rats. Hypoxia (7% inspired oxygen) evoked a typical increase in VE by either raising f and VT, ZnDPBG or its vehicle caused no change in basal VE and did not affect the increase in VE elicited by hypoxia. Conformably, i.c.v. heme-lysinate did not affect VE as well. These results do not support the hypothesis that the HO-CO pathway in the central nervous system is involved in hypoxia-induced hyperventilation.
authors.affiliation: Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto SP, Brazil.
authors.forename: Flávia M
authors.initials: FM
authors.lastname: Paro
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Steiner
authors.forename: Patricia M
authors.initials: PM
authors.lastname: De Paula
authors.forename: Luiz G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003905:Deuteroporphyrins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006418:Heme / Q000031:analogs & derivatives*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007276:Injections, Intraventricular; D008239:Lysine / Q000031:analogs & derivatives*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects; D013997:Time Factors; D014691:Ventilation / Q000379:methods
chemical_list: D003905:Deuteroporphyrins; D004791:Enzyme Inhibitors; C106087:heme lysinate; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D008239:Lysine