UCSF Team Identifies Gene Crucial To Blood Pressure

High blood pressure, or hypertension, affects nearly 60million American adults and is a leading cause of kidneyfailure. If uncontrolled, it also can damage major organs,such as the heart, brain, and arteries.

The gene, called sgk, mediates the effects of aldosterone, akey hormone for regulating sodium and water levelsthroughout the body. A disruption in the balance of thesefactors can result in blood pressure problems.

The researchers already knew that aldosterone was essentialto maintaining normal blood pressure, but its definitivelink 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. Thisholds the promise of providing better treatments for themillions of people with salt-sensitive hypertension," saidDavid Pearce, MD, UCSF assistant professor of medicine andcellular and molecular pharmacology, who treats patients atSan Francisco General Hospital Medical Center.

Pearce, who headed the research team, presented the findingshere today (June 13) at the annual meeting of The EndocrineSociety.

While hypertension is the most common blood pressuredisorder, there also are thousands of American adults whosuffer from low blood pressure, which can cause serioushealth consequences. Development of new treatments targetedat the regulation of sgk would be effective for both ofthese conditions, according to Pearce.

Blood pressure is the force of blood against the walls ofarteries in the body as it circulates to supply nutritionand oxygen to cells. Too high and the heart has to work toohard to pump blood through the vascular system; too low andblood doesn't move efficiently to all parts of the body.

The research team conducted the study in laboratory cellcultures using a cell line from animal kidney. The kidneyis a key organ in blood pressure regulation because itserves as the site where sodium is forwarded, as necessary,into the urine for elimination from the body. Sodium causesthe body to retain water, and blood is predominantly water.

High levels of sodium, therefore, can result in a highvolume of circulating blood. This condition in combinationwith already constricted blood vessels can lead to highblood pressure, Pearce explained. Aldosterone is the mostimportant member of a group of hormones calledmineralocorticoids, whose functions include transport ofsodium.

"Where sodium goes, so goes water, so aldosterone is key tothe maintenance of normal blood pressure," said Pearce.

The researchers used the technique called polymerase chainreaction, or PCR, to produce an unlimited quantity of DNAfor their study. The next step in their research is tolearn the factors that cause the skg gene to respond toaldosterone and if this process is affected by genemutations in patients, according to Pearce.

Study co-investigators are Aditi Bhargava, PhD; Sei-yuChen, PhD; David Rozansky, MD, PhD; Onno C. Meijer, PhD; andJim Wang, MD, all of UCSF; Patricia Buse, PhD, and GaryFirestone, 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 NationalInstitute of Diabetes and Digestive and Kidney Diseases.