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 (V t ) and pulmonary ventilation ( V e ) by body plethysmograph in conscious rats. Hypoxia (7% inspired oxygen) evoked a typical increase in V e by either raising f and V t . ZnDPBG or its vehicle caused no change in basal V e and did not affect the increase in V e elicited by hypoxia. Conformably, i.c.v. heme-lysinate did not affect V e 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.