Most brains are hardwired to call for extra oxygen when they need it, forcing the lungs to work overtime. But until recently, scientists couldn't figure out how this messaging system works and why it sometimes breaks down, especially in premature babies. Now, a team of researchers has discovered that nitric oxide, carried by hemoglobin, may signal the brain when oxygen is in short supply.
Oxygen and carbon dioxide are known regulators of respiration; when carbon dioxide builds up in the blood, your breathing rate goes up. But researchers have recently found that molecules called S-nitrosothiols (SNOs) play a key role, too. SNOs form when nitric oxide binds a specific amino acid within a protein. When more oxygen is needed in body tissues, these crucial molecules help widen blood vessels in the lungs, so that more oxygen can enter the bloodstream. This helps ensures that hemoglobin, the molecule red blood cells use to carry oxygen, gets fully loaded.
To clarify whether SNOs work on the brain, pulmonary specialist Benjamin Gaston of the University of Virginia School of Medicine, Charlottesville, and his colleagues injected certain SNOs into the brainstems of conscious rats. The rats breathed harder, even though their oxygen levels were normal. Then, to determine that SNOs are carried in the bloodstream, the scientists extracted two types of whole blood from the rats: blood containing hemoglobin molecules that were carrying oxygen, and those that had already delivered it. Because the SNOs are lighter than proteins, Gaston's group separated the heavy and light components of the blood. They injected the lighter, hopefully SNO-rich fractions of oxygen-free blood into the rats' brainstems and found that the rats breathed harder, just as before. Oxygenated blood had no effect. This implies that SNOs arise in the blood as oxygen is delivered to tissues. If the SNOs build up in the blood, that might signal the brain that oxygen is not being replaced fast enough.
"It is kind of surprising that respiration is controlled by something other than oxygen or carbon dioxide," says neurologist Stuart Lipton of the Burnham Institute in La Jolla, California. "This is the first time you can say there's a blood-borne SNO that actually influences the brain." By learning more about how SNOs are transported around the body, Lipton says, it should be possible to develop drugs that direct SNOs to parts of the brain.
Benjamin Gaston's page at the University of Virginia
Stuart Lipton's page at the Burnham Institute
Related article on SNOs and breathing from PNAS, May 2001
Nitric Oxide (NO), from Kimball's Biology Pages