Endogenous carbon monoxide in control of respiration

It is being increasingly appreciated that gas molecules such as nitric oxide (NO) function as chemical messengers in the nervous system. Recent studies suggest that carbon monoxide (CO) is another gas molecule that has similar biological actions as NO. The purpose of this article is to highlight the current information on the significance of endogenously generated CO in control of breathing. In mammalian cells, CO is generated during oxidative cleavage of heme by heme oxygenases (HO) and molecular oxygen is essential for this reaction. Two forms of HO have been identified including an inducible HO-1, that resembles stress-inducible protein HSP-32, and a constitutively expressed HO-2. HO-2 is expressed in many respiratory related neural structures including airway ganglion, carotid body, petrosal and nodose ganglia., nucleus of the tractus solitarius (nTS), and neurons of the rostral ventrolateral medulla (RVLM). Basal expression of HO-1 is either very low or even absent, but can be elevated during oxidative stress and hypoxia. Physiological studies have shown that CO might be of importance in vagally mediated contractions of airways. Several lines of evidence indicate that endogenously generated CO is a physiological modulator of the ventilatory response to hypoxia via its actions on carotid bodies and perhaps at brainstem neurons. In addition, CO might play a role in ventilatory adaptation to hypoxia, as low oxygen is a potent inducer of HO-1. Many of the neuronal structures that express HO also contain NOS, the enzyme that generates NO. Much remains to be studied on regulatory interactions between CO and NO and their impact on breathing.