June 16, 1999 SAN DIEGO -- Researchers from the University of California San Francisco have identified a gene that is critical in controlling blood pressure, a finding that could help in developing more effective therapies for hypertension.
High blood pressure, or hypertension, affects nearly 60 million American adults and is a leading cause of kidney failure. If uncontrolled, it also can damage major organs, such as the heart, brain, and arteries.
The gene, called sgk, mediates the effects of aldosterone, a key hormone for regulating sodium and water levels throughout the body. A disruption in the balance of these factors can result in blood pressure problems.
The researchers already knew that aldosterone was essential to maintaining normal blood pressure, but its definitive link with the sgk gene had not been made.
"Now that we know that sgk mediates aldosterone's effects, we can begin to devise ways of blocking its action. This holds the promise of providing better treatments for the millions of people with salt-sensitive hypertension," said David Pearce, MD, UCSF assistant professor of medicine and cellular and molecular pharmacology, who treats patients at San Francisco General Hospital Medical Center.
Pearce, who headed the research team, presented the findings here today (June 13) at the annual meeting of The Endocrine Society.
While hypertension is the most common blood pressure disorder, there also are thousands of American adults who suffer from low blood pressure, which can cause serious health consequences. Development of new treatments targeted at the regulation of sgk would be effective for both of these conditions, according to Pearce.
Blood pressure is the force of blood against the walls of arteries in the body as it circulates to supply nutrition and oxygen to cells. Too high and the heart has to work too hard to pump blood through the vascular system; too low and blood doesn't move efficiently to all parts of the body.
The research team conducted the study in laboratory cell cultures using a cell line from animal kidney. The kidney is a key organ in blood pressure regulation because it serves as the site where sodium is forwarded, as necessary, into the urine for elimination from the body. Sodium causes the body to retain water, and blood is predominantly water.
High levels of sodium, therefore, can result in a high volume of circulating blood. This condition in combination with already constricted blood vessels can lead to high blood pressure, Pearce explained. Aldosterone is the most important member of a group of hormones called mineralocorticoids, whose functions include transport of sodium.
"Where sodium goes, so goes water, so aldosterone is key to the maintenance of normal blood pressure," said Pearce.
The researchers used the technique called polymerase chain reaction, or PCR, to produce an unlimited quantity of DNA for their study. The next step in their research is to learn the factors that cause the skg gene to respond to aldosterone and if this process is affected by gene mutations in patients, according to Pearce.
Study co-investigators are Aditi Bhargava, PhD; Sei-yu Chen, PhD; David Rozansky, MD, PhD; Onno C. Meijer, PhD; and Jim Wang, MD, all of UCSF; Patricia Buse, PhD, and Gary Firestone, PhD, of UC Berkeley; and Luca Mastroberardino, PhD, and Francois Verrey, MD, of the University of Zurich, Switzerland.
The research was supported in part by a grant from National Institute of Diabetes and Digestive and Kidney Diseases.
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