Antioxidants, Stress and Hypertension: Researchers Seek Answers to Fundamental Questions
The Medical College of Wisconsin (MCW) has received a five-year, $9.5 million grant from the National Institutes of Health’s National Heart, Lung and Blood Institute to study the role of hydrogen peroxide in development of salt-sensitive hypertension.
Allen Cowley, PhD, professor and chair of physiology at MCW, is the primary investigator of the program project grant. Co-primary investigators are David Mattson, PhD, professor of physiology; and Mingyu Liang, PhD, MB, professor of physiology. Dr. Cowley holds the James J. Smith & Catherine Welsch Smith Chair in Physiology, and Harry & Gertrude Hack Term Chair in Physiology, at MCW.
Nearly one out of three American adults has hypertension, or high blood pressure (78 million). It is the primary cause of death for 62,000 people in the U.S. every year, and a contributing factor in more than 348,000 deaths. Many of the mechanisms contributing to hypertension are still unknown; however, in 30-50% of people, ingestion of salt contributes to a rise in blood pressure.
The unifying hypothesis of this program project grant centers on the concept that hydrogen peroxide production in the part of the kidney called the renal outer medulla plays a dominant role in the development of salt-sensitive hypertension.
In the first project, Dr. Cowley’s team will explore the hypothesis that increased salt intake results in excess production of hydrogen peroxide, which constricts the blood vessels of the kidney. Dr. Mattson’s team suspects that constriction leads to an initial increase in arterial pressure, which results in an increase of free radicals and cytokines in the kidney. Finally, Dr. Liang’s team will evaluate the hypothesis that a newly discovered pathway of hydrogen peroxide production related to metabolism contributes importantly to the development of hypertension.
The conceptually unique, yet correlated hypotheses will advance understanding of the molecular and physiological mechanisms underlying salt-sensitive hypertension. Additionally, the studies will provide a better understanding of the mechanisms responsible for increased oxidative stress and enable the targeting of enzymes responsible for its generation, which should lead to better antioxidant therapies.