Related Experiment Video
Updated: Sep 28, 2026

Experimental Approach to Examine Leptin Signaling in the Carotid Bodies and its Effects on Control of Breathing
Published on: October 25, 2019
Central heme oxygenase-carbon monoxide pathway in the control of breathing under normoxia and hypoxia
Flávia M Paro1, Alexandre A Steiner, Patricia M De Paula
1Departamento de Morfologia, Estomatologia e Fisiologia, Faculdade de Odontologia de Ribeirão Preto, Ribeirão Preto SP, Brazil.
Insights
The central heme oxygenase-carbon monoxide pathway does not influence breathing responses to low oxygen. This study found no evidence that this pathway regulates hypoxia-induced hyperventilation in rats.
Area of Science:
- Physiology
- Neuroscience
- Biochemistry
Background:
- Endogenous carbon monoxide (CO) is produced from heme catabolism by heme oxygenase (HO).
- The central nervous system's role in regulating respiratory responses to hypoxia is complex.
- The heme oxygenase-carbon monoxide (HO-CO) pathway is a potential regulator of physiological processes.
Purpose of the Study:
- To investigate the involvement of the central HO-CO pathway in hypoxia-induced hyperventilation.
- To test if inhibiting or inducing the HO-CO pathway affects respiratory control during low oxygen conditions.
Main Methods:
- Conscious rats were administered intracerebroventricular (i.c.v.) injections of a HO inhibitor (ZnDPBG) or heme-lysinate.
- Respiratory frequency (f), tidal volume (VT), and pulmonary ventilation (VE) were measured using body plethysmography.
- Hypoxia was induced using 7% inspired oxygen.
Main Results:
- Hypoxia significantly increased pulmonary ventilation (VE) by elevating respiratory frequency (f) and tidal volume (VT).
- Neither the HO inhibitor (ZnDPBG) nor heme-lysinate altered basal VE or the hyperventilatory response to hypoxia.
- Vehicle administration also did not affect respiratory parameters.
Conclusions:
- The central heme oxygenase-carbon monoxide pathway does not appear to play a significant role in mediating the respiratory response to acute hypoxia in rats.
- These findings do not support the hypothesis that the HO-CO pathway is involved in hypoxia-induced hyperventilation.
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.
More Related Videos
Related Concept Videos
Physiological Control of Respiration
Breathing, a seemingly passive process, is regulated by the respiratory center in the brainstem. This center coordinates the involuntary control of respirations, which means it occurs without conscious effort, ensuring a smooth and uninterrupted pattern.
Regulation of Ventilation
The body maintains ventilation by monitoring levels of carbon dioxide (CO2), oxygen (O2), and hydrogen ion concentration (pH) in the arterial blood. Among these factors, the level of CO2 plays a crucial...
Chemical Factors Affecting Respiration Centers
CO2 has a potent influence on respiration and is strictly regulated. Under...
Hypoxia
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Oxygen Transport in the Blood
Physiology of Respiration II: Neurogenic Control of Respiration
Central Control
The brainstem is the primary site of central control, hosting respiratory centers:
Respiration and Gaseous Exchange
Respiration involves the exchange of gases, especially oxygen (O2) and carbon dioxide (CO2), between the alveoli and body cells, a process facilitated by blood circulation. As a result, the cardiovascular system, which involves the...

