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Hypertension: Hot on the Trail of a Silent Killer

June 17, 2009

By: Jennifer Alexander

Note: This story originally appeared in the 2008 issue of Baylor Research magazine published by the Office of the Vice Provost for Research at Baylor.

Picking up where he left of more than 25 years ago at Johns Hopkins School of Medicine, Dr. William D. Hillis and several Baylor students are engaging in research that will help physiologists understand the mechanisms by which hypertension may be generated in the human body.

"All this work has been made possible by the availability of FRIP [Faculty Research Investment Program] funding," which was awarded in May 2005, Hillis says. "I was fortunate to have had the assistance of 12 undergraduate students in this work, all of whom were the principal investigators."

The FRIP grant also provided Hillis with the equipment needed to carry out his research. Hillis, the Cornelia Marschall Smith Distinguished Professor of Biology, works primarily with pre-medical candidates. Together they have been growing rat adrenal (zona glomerulosa) cells in vitro to determine the effects that known stimulators and inhibitors have on the cells' aldosterone production. Aldosterone is a steroid hormone that regulates sodium, potassium and fluid balance in the blood.

"We've found that potassium directly stimulates the production of aldosterone - something that has long been expected on the basis of clinical experience," says Hill is. To his knowledge, he adds, it had not previously been demonstrated to be directly responsible for enhancing aldosterone production.

For one undergraduate, the research project was a testament to Hillis' desire to let students learn from their mistakes. Senior biology major Eileen Follett signed up for the team after meeting with Hillis, though she'd never taken his class. "I was in the midst of writing my honors thesis, and I had to do research for it," Follett recalls. "There is almost no research like this being done."

The lab work, which involved extracting collagen from rat tails, mixing it with acetic acid to solubilize it, reconstituting it by neutralization, and finally allowing adrenal cells to grow on it, was Follett's first foray into self-guided testing. The students then divided into teams to test the effects of different hormones and chemicals on aldosterone production by the adrenal cells.

As a relative newcomer to the research experience, Follett says, "I can't tell you how many times I started over." But, she adds, she appreciates Hillis' willingness to let the students take the lead on such a groundbreaking project. As a result of last year's work, Follett's thesis now centers on the project: She is examining how, and why, a certain hormone affects aldosterone production.

In his research, Hillis found that the hormone angiostensin II also contributes to an increase in aldosterone production. Angiostensin II is basically produced by the enzyme renin, which is released from kidney cells when they experience low oxygen availability. Hillis says his findings will indirectly affect clinical practice in the care of hypertension and will allow him to begin the next step of research, which is to determine whether other hormones, neurotransmitters or neuromodulators will have an affect on aldosterone production.

According to Hillis, the renin-angiotensio-aldosterone axis is a system that apparently contributes frequently to the genesis of essential hypertension, a disease that presents itself in 50 to 60 percent of older Americans. "I would love to find a biologically active substance that would inhibit aldosterone production," he says, "in which case it might be useful as a possible therapeutic mode to test clinically whether it might ameliorate hypertension."