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A single mechanism for hypertension, insulin resistance and immune suppression
Date:6/29/2008

neously from hypertension, diabetes, and other metabolic conditions, said Schmid-Schnbein.

The team went on to test whether administration of a protease-blocking drug could reverse the multiple metabolic complications in the rat strain. They administered doxycycline, a seemingly unlikely candidate to have such a beneficial effect. Infectious disease specialists often prescribe doxycycline, an antibiotic, to counter bacterial infections. However, in laboratory tests doxycycline also blocks the activity of certain proteases in the SHR strain of rat.

The researchers found that protein receptors on the surface of SHR cells become clipped off as the animals develop hypertension. They used a novel visualization technique to show 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. 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, Schmid-Schnbein said. Our observations provide a conceptual framework in which we can start to understand how diverse complications in the metabolic syndrome arise.

Schmid-Schnbein said his findings will likely spark follow-up studies of this mechanism in humans.

Even if future studies only support the clear linkage of hypertension to insulin receptor cleavage in the current study of SHRs, this observation should lead to many studies of how these two problems perhaps interact, wrote Bohlen in the Hypertension editorial. To what extent this interaction is part of the cause or consequences of mechanisms associated with hypertension will remain controversial for som
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Contact: Rex Graham
ragraham@ucsd.edu
858-822-3075
University of California - San Diego
Source:Eurekalert  

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