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Mechanisms Leading To Portal Hypertension Uncovered

Date:
September 30, 2005
Source:
UT Southwestern Medical Center
Summary:
A physician-scientist at UT Southwestern Medical Center and his research team have identified mechanisms causing a potentially deadly type of hypertension that results from liver damage -- findings that could lead to its prevention. This particular type of hypertension, called portal hypertension, affects the blood flow into the portal vein, which feeds blood to the liver.

Dr. Don Rockey, chief of the division of digestive and liver diseases at UT Southwestern, has reported new findings on a potentially deadly form of hypertension that results from liver damage.
Credit: Image courtesy of UT Southwestern Medical Center

A physician-scientist at UT Southwestern Medical Center and his research team have identified mechanisms causing a potentially deadly type of hypertension that results from liver damage - findings that could lead to its prevention.

This particular type of hypertension, called portal hypertension, affects the blood flow into the portal vein, which feeds blood to the liver.

Dr. Don Rockey, the new chief of the digestive and liver diseases at UT Southwestern, identified the cellular activity that results in portal hypertension. He and his colleagues then took the research a step further, showing that if the process can be interrupted, the hypertension subsides.

The National Institutes of Health-funded research - available online and scheduled to appear in a future issue of the journal Nature Medicine - was conducted by Dr. Rockey while he was at Duke University Medical Center.

"Portal hypertension is a deadly disease that complicates many forms of chronic liver injury," Dr. Rockey said. "When this occurs, in its most severe form, the prognosis definitely becomes guarded," often leading to the need for a liver transplant.

The short-term mortality for patients with portal hypertension is about 30 percent. The latest research opens new ground scientifically and has implications for possible clinical approaches, said Dr. Rockey.

"The end result of portal hypertension is bleeding and development of ascites [fluid in the abdomen]; so if you could treat it early, you could prevent bleeding and/or the formation of ascites," he said.

Portal hypertension is similar to the widely known essential hypertension, which impairs blood flow to the heart systems. But portal hypertension affects blood flow to the liver-related systems.

The liver is an essential organ that washes the body's blood of wastes and poisons. Cirrhosis of the liver occurs when the cells are damaged. Scarring often results, reducing blood flow into the liver and raising pressure on veins not designed to handle that much blood flow. The high pressure can cause veins to burst, resulting in internal bleeding and potentially death.

Previous studies have shown that, at the cellular level, portal hypertension results from reduced production of needed nitric oxide, which regulates expansion of the blood vessels.

Dr. Rockey's research identified how the nitric oxide production breaks down due to the effects of the protein GRK2. The protein attaches to another protein called AKT, interrupting the creation of nitric oxide.

"We've shown that the endothelial cells that line the blood vessels in the liver don't work quite right. Specifically, they don't produce nitric oxide," Dr. Rockey said. "The problem is that there are a number of signaling pathways that are disrupted and that results in the reduced production of nitric oxide."

In addition to identifying how the system breaks down, Dr. Rockey's study showed that reducing the GRK2 production restored AKT production, allowing nitric oxide levels to stabilize and blood pressure to return to normal.

Further research will be needed, Dr. Rockey said, to determine how to control GRK2 proteins that interfere with AKT or ways to bolster AKT protein production to maintain nitric oxide production.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

UT Southwestern Medical Center. "Mechanisms Leading To Portal Hypertension Uncovered." ScienceDaily. ScienceDaily, 30 September 2005. <www.sciencedaily.com/releases/2005/09/050930083357.htm>.
UT Southwestern Medical Center. (2005, September 30). Mechanisms Leading To Portal Hypertension Uncovered. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2005/09/050930083357.htm
UT Southwestern Medical Center. "Mechanisms Leading To Portal Hypertension Uncovered." ScienceDaily. www.sciencedaily.com/releases/2005/09/050930083357.htm (accessed April 18, 2014).

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