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Discovery of Nitric Oxide Delivery Mechanism May Lead to New Treatments for Hypertension

Finding could have wide-ranging implications, researchers say (Nov. 13)

Researchers at the University of Virginia School of Medicine have shed new light on blood pressure regulation with the discovery of an unexpected mechanism by which hemoglobin controls the delivery of nitric oxide (NO). The findings may point to a new therapeutic target for treating hypertension and may have implications for many organ systems and illnesses.

Hemoglobin is best known for its role in transporting oxygen in the blood, but it also can bind NO, a powerful vasodilator. By relaxing smooth-muscle cells, NO widens blood vessels, thereby decreasing blood pressure. The new research shows that there is a complete system within the myoendothelial junction — the “bridge” between the smooth muscle and the endothelial cells lining the blood vessel walls — that allows hemoglobin to regulate NO delivery, essentially controlling the size of the blood vessel.

The researchers were surprised to find hemoglobin alpha in the myoendothelial junction. At first they thought it was a mistake. They had seen reports of hemoglobin alpha from other researchers who looked at myoendothelial junctions, but it would typically be one protein in a list of many, reported for the sake of completeness. The researchers, however, realized that hemoglobin alpha was actually regulating the binding of NO, thereby directly affecting the size of the blood vessel.

Some chronic problems with hypertension may be the result of problems with the amount of hemoglobin in the blood-vessel wall, according to Dr. Brant Isakson.

“The implications for this research are very widespread,” he said. “The most immediate thing is blood pressure regulation. We’re trying to find ways to specifically delete hemoglobin alpha in the blood vessel wall and look at blood pressure changes.”

But the mechanism the researchers have identified may play an important role in many other parts of the body, and possibly in many illnesses.

“There are all these scattered reports of hemoglobin and [nitrogen oxide signaling] expressed in the lungs, for example, and in neurons, and in all these other places,” Isakson said. “Maybe, just maybe, it’s very similar to what we show here: that they form this macromolecular complex, and that can very tightly regulate how much nitric oxide is delivered.”

“In our case,” Isakson continued, “we’re very interested in how that nitric oxide regulates blood pressure and dilates the smooth muscle. But you can extrapolate that to neurons. Neurons use nitric oxide for their cell communication. Inflammatory responses — there’s another big one. Nitric oxide is anti-inflammatory. We’re really extrapolating here, but if we are correct — if you can regulate how much nitric oxide is released by this complex — then you can regulate the inflammatory response.”

The new findings were published online in Nature.

Source: University of Virginia; November 13, 2012.

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