Single mechanism underlying hypertension, insulin resistance, immune suppression identifiedJune 30th, 2008 - 5:43 pm ICT by ANI
Washington, June 30 (ANI): A study on rats has led to the discovery of a mechanism that may help scientists understand why metabolic disorders like hypertension, insulin resistance, and immune suppression arise together in mammals.
The study conducted by bioengineering experts at UC San Diegos Jacobs School of Engineering has also revealed that a drug may effectively counteract the underlying molecular mechanism.
Writing about their findings in the online version of Hypertension, the researchers have revealed that they predisposed rats to develop high blood pressure for their study, and named them the spontaneously hypertensive rat (SHR).
The researchers believe that their study will likely be important to people suffering from obesity as well as hypertension.
With the national and international emphasis on obesity and its attendant cardiovascular problems, there is a tendency to forget that essential hypertension affects about the same percentage of humans as does serious obesity and an even higher percentage of the population than does type 2 diabetes mellitus, H. Glenn Bohlen, a professor in the Department of Cellular and Integrative Physiology at Indiana University Medical School, wrote in an accompanying editorial in Hypertension.
The elegant study by (Frank) Delano and (Greet) Schmid-Schonbein points to a potentially very important overlap of an insulin resistance mechanism with hypertension in the spontaneously hypertensive rat (SHR), Bohlen wrote.
During the study, the researchers found significant levels of proteases, which are enzymes that break down proteins, among the SHR rats.
We were looking for a common cause of diverse but concurrent metabolic problems and we were testing our theory that enhanced proteolytic activity in the circulation may be the root cause. In the hypertensive rat we studied, enzymes cleave extracellular portions of several protein receptors, such as the insulin receptor, so that insulin can no longer bind and facilitate normal metabolism of glucose, said Schmid-Schonbein, a professor of bioengineering.
The study showed that the SHR animals had protease activity in their circulation that cleaves more than just insulin receptors.
According to the researchers, proteases in such animals also cleave significant numbers of CD18, an important binding receptor on the surface of infection-fighting leukocytes.
They said that with the loss of CD18 receptors, leukocytes of the SHR animals are unable to bind to the wall of blood vessels, resulting in a compromised immune system.
These results point to a single mechanism that explains multiple and diverse cell dysfunctions encountered in hypertensive rats, and they also suggest that a similar mechanism may be operating in humans suffering simultaneously from hypertension, diabetes, and other metabolic conditions, said Schmid-Schonbein.
The researchers then set out to determine whether a protease-blocking drug could reverse the multiple metabolic complications in the rat strain, and administered the rats an antibiotic called doxycycline which doctors often prescribe to counter bacterial infections.
They found that protein receptors on the surface of SHR cells become clipped off as the animals develop hypertension.
Using a novel visualization technique, the researchers showed that after several weeks of ingesting doxycycline in their drinking water, the SHR rats developed cells that again bristled with normal CD18 and insulin receptors.
They said that the animals metabolic conditions simultaneously improved, blood pressure normalized, and symptoms of immune suppression disappeared.
These studies indicate the first time that hypertension and cell dysfunctions associated with the metabolic syndrome may be part of an enzymatic auto-digestion process in which proteases in our body become uncontrolled and break down proteins. Our observations provide a conceptual framework in which we can start to understand how diverse complications in the metabolic syndrome arise, Schmid-Schonbein said.
He said that his findings would likely spark follow-up studies of this mechanism in humans. (ANI)
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