To test the role of PPAR in edema, Yang created mice that specifically lacked PPAR-gamma in the collecting duct. He then administered TZD to these mice, as well as to a control group that didn't lack PPAR-gamma.

The mice not lacking PPAR-gamma showed about a 10 percent average increase in body weight because of fluid retention. The blood plasma volume of these mice increased by one-third, Yang said. But the mice bred without PPAR-gamma experienced no increase in body weight in response to the drug, according to Yang.

"This tells us that the body weight gain is regulated by PPAR-gamma in the collecting duct," he said. "We also found this drug decreased the sodium excretion in urine, so this could explain the fluid retention."

The mice without PPAR in the collecting ducts incurred no changes in sodium reabsorption, while those with PPAR excreted less sodium through urination. Yang said that the distal nephron, which is usually subject to hormone regulation in the kidney, serves as a key pathway for keeping an accurate amount of sodium in the body.

Hypertension affects one in four U.S. adults and long had been considered a cardiovascular disease. But research now also focuses on the kidneys and the role of the distal nephron in retaining sodium opens a new area for study, he said.

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Contact: Phil Sahm
Phil.Sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences Center
17-Jun-2005