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Nitric oxide heart

Professor Jonathan Stamler's latest findings regarding nitric oxide have the potential to reshape fundamentally the way we think about the respiratory system - and offer new avenues to save lives. It may be time to rewrite the textbooks.

Scientific dogma has the respiration process involving only two elements—oxygen and carbon dioxide. Specifically, the delivery of oxygen from lungs to tissues, and the removal of the waste product, carbon dioxide, through exhaling.

Recently published online in the journal Proceedings of the National Academy of Sciences (PNAS), Stamler and colleagues demonstrate that nitric oxide is essential for the delivery of oxygen to the cells and tissues that need it.

Stamler, MD, a Professor of Medicine at Case Western Reserve University School of Medicine and Cardiologist at University Hospitals Case Medical Center, led a team that showed that nitric oxide must accompany hemoglobin to enable blood vessels to open and then supply oxygen to tissues.

Doctors have long known that a major disconnect exists between the amount of oxygen carried in the blood and the amount of oxygen delivered to the tissues. Until now, they had no way to explain the discrepancy. The new findings show that nitric oxide within the red blood cell itself is the gatekeeper to the respiratory cycle - nitric oxide makes the cycle run.

"The bottom line is that we have discovered the molecular basis of blood flow control in the respiratory cycle loop, " Stamler said. "It's in the hemoglobin protein itself, which has the ability to deliver the nitric oxide together with oxygen. The simplified textbook view of two gases carried by hemoglobin is missing an essential element - nitric oxide - because blood flow to tissues is actually more important in most circumstances than how much oxygen is carried by hemoglobin. So the respiratory cycle is actually a three-gas system."

Stamler's previous research had revealed that the respiratory cycle was more than an oxygen and carbon dioxide exchange proposition. Stamler and colleagues also had shown that red blood cells carry and release nitric oxide, but had not yet explained the exact physiologic ramifications of nitric oxide release.

In this most recent research, investigators uncovered the key role of nitric oxide in controlling the blood flow in small vessels within tissues responsible for delivering oxygen (known as "blood flow autoregulation") - a process whose molecular basis had been a longstanding mystery in medicine. Investigators specifically examined the respiratory cycle in mice lacking the one amino acid site that carries nitric oxide in their red blood cells. Low and behold, blood flow autoregulation was eliminated entirely - the animals could not oxygenate tissues.

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