July 2008

A New Route to High Blood Pressure

Hypertension can be caused by abnormalities in blood vessels, researchers find, leading to possibility for new treatments

A recently discovered cause of high blood pressure may lead to new possibilities for treating the disease, which puts some 65 million Americans at higher risk for heart attack, stroke and other life-threatening health problems.

"Our results suggest that dysfunction in this [blood vessel] system may well be an important underlying cause of cardiovascular disease in humans," says Simon K. Michael, an assistant professor of pediatrics at the medical school. Photo: Wolfgang Amri/iStock

Tufts researchers found that abnormalities in blood vessels-rather than just the kidneys, as had been thought-can be a primary cause of high blood pressure. The findings are significant for people whose high blood pressure is not linked to a specific cause.

"These results suggest a potential paradigm shift in the field of hypertension," says Howard K. Surks, an assistant professor of medicine at Tufts and co-author of the study, which was recently published in the Proceedings of the National Academy of Science.

"Previously, all causes of hypertension were thought to arise from the kidney, but that assumption was based on extremely rare genetic causes that do not pertain to the vast majority of patients with high blood pressure," says Surks. "Our data suggest that an abnormality in the blood vessel that does not affect kidney function can also cause high blood pressure."

The finding, he notes, validates efforts being made to find new targets for the treatment of hypertension in blood vessels.

The Mechanics of High Blood Pressure

For the study, the researchers developed a slightly altered form of a protein called PKG, which occurs naturally in the body and helps to relax smooth muscle cells in blood vessel walls. It was engineered to not interact with an enzyme in mice blood vessel cells that enables blood vessel walls to dilate and thus lower blood pressure.

The study found the breakdown in this molecular-level communication system led to hypertension. Extra care was taken to rule out renal causes of high blood pressure in the mice in the study.

As with mice, healthy human blood vessels contain PKG, which enables their blood vessels to dilate properly to lower blood pressure. When blood vessels cannot dilate sufficiently as blood circulates through the body, blood pressure increases, leading to a host of medical problems, including stroke, heart attacks, kidney failure and heart failure.

"In a very real sense, the single cell layer which lines all blood vessels in the human body, the endothelial cell layer, can be thought of as an organ system in its own right," says Simon K. Michael, an assistant professor of pediatrics at the medical school and co-author of the paper.

"Our experiments have disrupted an important communication pathway between the endothelial cell and the underlying cells of the blood vessel wall," he says. "Our results suggest that dysfunction in this system may well be an important underlying cause of cardiovascular disease in humans. In retrospect, this seems quite intuitive."

The Tufts researchers are now examining human DNA to determine if abnormalities in PKG or other related blood vessel proteins exist in people with high blood pressure.

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