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Mutation plays key role in hypertension

A gene mutation of a key enzyme that regulates smooth muscle contraction and blood pressure in rats has been identified by researchers at the University of Illinois at Chicago. The finding, the first genetic link to muscle contraction and high blood pressure, may lead to improved treatments for hypertension.

The study appears in the September issue of Molecular Biology of the Cell.

When myosin, a protein that is abundant in muscle and is necessary for muscle contraction, is activated, smooth muscle cells in blood vessel walls contract and raise blood pressure. The cells also proliferate, thickening the walls and narrowing the channel, further increasing blood pressure.

Together, this results in hypertension, according to Dr. Primal de Lanerolle, professor of physiology and biophysics and senior author of the study. The current crop of drugs used to treat hypertension mainly targets contraction of the smooth muscle cells. They do not affect the proliferation of the cells, and the thickening of the walls of blood vessels is presently irreversible.

In the new study, the researchers were able to confirm the increased levels of the activated form of myosin in hypertensive rats, a widely used animal model of hypertension. More importantly, they established why myosin activation is elevated and linked the mechanism to a gene mutation.

The researchers found there was more of a protein called smooth muscle myosin light chain kinase, which activates myosin, in their hypertensive rats than in closely related rats that do not develop hypertension. They also found that there was more of the kinase's messenger RNA, the genetic message the cell uses to make the kinase.

"This told us that whatever was happening to raise levels of the kinase was happening at a genetic level," de Lanerolle said.

Although secondary hypertension may result from another disorder or from some medications, essential hypertension --
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Contact: Jeanne Galatzer-Levy
jgala@uic.edu
312-996-1583
University of Illinois at Chicago
13-Sep-2006


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