Does stress increase blood pressure? This simple question has been the focus of intense research for many years. Now new research has for the first time established a link between a novel gene, phosducin, and the blood pressure response to stress in mice as well as humans. The studies were directed by scientists at the University of Freiburg and Muenster in Germany, and the Medical College of Wisconsin in Milwaukee, in collaboration with other institutions in Europe and Canada. The results are published online in the Journal of Clinical Investigation in advance of the print publication.
The German team, led by Lutz Hein M.D., in collaboration with Monika Stoll, Ph.D., generated mice lacking the phosducin gene and compared them with normal mice. The mice lacking this gene developed high blood pressure under various conditions of stress. The mechanism of this gene's action appears to be directly involved with specific sympathetic nerve cells The cells show a distinct increase in their activity translating into an increase in blood pressure.
The findings were then tested using DNA from 342 African Americans enrolled in an ongoing high blood pressure study at the Medical College, and 810 French Canadians at the University of Montreal. The volunteers were then asked to perform certain standardized stress-related activities which confirmed the beneficial action of the gene in humans. In African Americans as well as French Canadians, certain phosducin DNA variants serve as markers and can identify patients with an increase blood pressure response, for example when taking a math test. Additional cohorts from Europe also confirm this relationship with regard to blood pressure.
"These studies provide us with unique insights into the mechanisms of blood pressure stress response and will provide a novel target for the treatment of this distinct form of high blood pressure," says Ulrich Broeckel, M.D., associate professor of pediatrics, medicine, and physiology, and chief of pediatric genomics at the Children's Research Institute.
Analysis in humans indicated that a number of phosducin gene variants were associated with certain stress-dependent blood pressure responses. Further, one gene variant in particular was associated with elevated baseline blood pressure. These data led the authors to suggest that phosducin might be a good target for drugs designed to alleviate stress-induced high blood pressure.
Dr. Broeckel conducted these studies in collaboration with Ted Kotchen, M.D., associate dean for clinical research; Allen Cowley, Ph.D., Chairman and Harry & Gertrude Hack Term Professor in Physiology; and James J. Smith and Catherine Welsch Smith Professor in Physiology; and Howard Jacob, Ph.D., Warren P. Knowles Professor in Human and Molecular Genetics and director of the Center at the Medical College. Other collaborators were Michael Harrison, graduate physiology student, as well as Dr. P. Hamet at the University of Montreal.
In an accompanying commentary, however, Guido Grassi, at Clinica Medica, Italy, notes that further studies are needed before the therapeutic implications of these data can really be determined.
- Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice. Journal of Clinical Investigation, November 23, 2009
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