A collaborative study by researchers at the University of Vermont College of Medicine and Stanford University has found that high blood pressure can result from a defect in a component of the muscle cells in the walls of blood vessels. This component, called the "beta 1 subunit," regulates a protein that controls the constriction and dilation of arteries. High blood pressure is a leading risk factor for stroke and heart disease. A report on these findings, titled "Vasoregulation by the beta 1 subunit of the calcium-activated potassium channel," will be published in the Oct. 19, 2000 issue of the international scientific journal Nature. This new finding could have an impact on the development of future blood pressure treatments. To identify the chain of events that leads blood vessels to constrict so tightly that blood pressure is elevated, the researchers focused their attention on molecular changes in the "smooth" muscle cells of artery walls. When these muscle cells relax, the arteries become wider or "dilate." Activation of a protein called the "calcium-activated potassium channel" in the smooth muscle cells can cause arteries to dilate. These calcium-activated potassium channels are composed of smaller proteins called alpha and beta 1 subunits. For the purpose of this study, the Stanford research team bred mice that do not manufacture the beta 1 subunit protein. UVM researchers then examined the function of calcium-activated potassium channels in smooth muscle cells in arteries from the brains of these mice. These scientists found that, without the beta 1 subunit gene, the function of the calcium-activated potassium channel is disabled, thus leading to a constriction of the arteries and elevated blood pressure. Senior study authors Richard Aldrich, Ph.D., an investigator at the Howard Hughes Medical Institute at Stanford University, and Mark Nelson, Ph.D., chair of UVM's Department of Pharmacology, began this research a little less than 18 months ago. The study's focus followed research on "calcium sparks," discovered by Nelson and published in a 1995 paper in the journal Science. These sparks were identified as the basic signaling elements that can cause dilation of arteries through stimulation of calcium-activated potassium channels. "These results have implications not only for the treatment of high blood pressure, but in other areas - such as the bladder and lungs - where overly contracted smooth muscle causes conditions such as incontinence and asthma," said Nelson. In addition to Nelson, the UVM study team includes Adrian Bonev, Ph.D., Delrae Eckman, Ph.D., and Guillermo Perez, Ph.D., of the UVM College of Medicine's department of pharmacology. Funding for this study came from the National Institutes of Health (National Heart, Lung and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases), the National Science Foundation, the Totman Medical Trust for Cerebrovascular Research, the American Heart Association, the Federation for Anesthesia Education and Research, and the Howard Hughes Medical Institute at Stanford University.