By Sean Henahan, Access Excellence

MILWAUKEE, WI-(5/22/96) The discovery that inherited defects in the kidney set the stage for hypertension, comes as a major surprise to researchers who had believed the opposite hypothesis- that high blood pressure led to kidney defects.

Researchers at the Medical College of Wisconsin looked at this 'chicken and egg' question: which comes first, high blood pressure or loss of kidney function?, over a ten year period. Their work indicates that an inherited defect in the control of kidney function comes first, and this raises blood pressure.

Conventional medical thought has been that elevated blood pressure of unknown origin, known as essential hypertension, damages the kidneys. No, say Allen Cowley, Ph.D., professor and chairman of physiology, and Richard Roman, Ph.D., professor of physiology. "Subtle defects in kidney function are the cause of hypertension; the genes that cause the disease are genes that regulate kidney function," said Dr. Cowley.

They have also located a new apparent source of the problem by peering into a previously hidden area of the blood supply to the kidney.

According to Dr. Roman, the human cardiovascular system is like a loop-shaped, fluid- filled tube. Every day we eat salt and drink water, putting more volume into the system. The kidneys, he said, act like check valves; they sense the pressure in the system and let out the same amount of fluid you take in. "What comes in, must equal what goes out. That's how the system is regulated," he said.

What happens if the kidneys don't excrete the same amount of fluid that comes in each day? The same thing that would happen if you kept pumping air into a tire without letting any out. Eventually the pressure builds up. That, Dr. Roman said, is the cause of high blood pressure.

Increased blood pressure from fluid buildup causes a normal kidney to excrete more salt and water to maintain the critical balance. But in a person with hypertension that system goes awry. They have identified a number of things that can cause failure in the check valve function of the kidneys: a problem in the blood vessels so the kidneys don't get a sense of the pressure in the body, or a defect in the hormones that "talk to" the kidneys.

The researchers in the hypertension project set out to prove their theory that kidney defects cause high blood pressure. Medical thought at the time said that high blood pressure was a vascular disease - constricted blood vessels make the size of the container smaller so pressure builds up. According to Drs. Cowley and Roman's theory, the size of the container shouldn't matter - the kidneys should be able to adjust the amount of fluid in the body to restore normal pressure.

"We studied many models of hypertension in animals, and we found that in every model, the hypothesis that there is an abnormality in kidney function stood up," said Dr. Cowley.

More recently the researchers have been looking at the mechanism of just how the kidneys sense blood pressure and increase excretion. "We have developed ways to study blood flow in a place deep within the kidney that physicians haven't been able to see into in the past, called the inner medulla," said Dr. Roman. "This is where we found the sensor for blood pressure control in the kidney. We showed that if you narrow the vessels in just this area of the kidney in rats, you produce the disease."

Dr. Roman does not foresee genetic therapy for high blood pressure in the near future, especially since there are lifestyle modifications and drugs that can control the disease once it is diagnosed. Instead, he said, once they locate the specific genes that cause the defect (he thinks there could be as many as 20 or 30), people will be screened to see if they carry one of these genes. If so, by changing their lifestyle, especially controlling salt in the diet, they may be better able to prevent development of the disease. Rats with a faulty kidney gene usually die in a few weeks of heart attacks or stroke when they are fed a high salt diet, but if they stay on a no-salt diet they never get hypertension and live much longer.

The study appeared in the May 22 issue of the Journal of the American Medical Association.

Related information on the Internet

JAMA Hypertension Issue

American Heart Association

National Institute of Diabetes and Digestive and Kidney Disease

The Human Kidney Online