Researchers identify new pathway linking the brain to high blood pressure

Discovery could eventually lead to new treatments for hypertension and heart failure

New research by scientists at the Ottawa Heart Institute and the University of Maryland School of Medicine (UM SOM) has uncovered a new pathway by which the brain uses an unusual steroid to control blood pressure. The study, which also suggests new approaches for treating high blood pressure and heart failure, appears today in the journal Public Library of Science (PLOS) One.

"This research gives us an entirely new way of understanding how the brain and the cardiovascular system work together," said Dr. John Hamlyn, professor of physiology at the University of Maryland School of Medicine, one of the principal authors. "It opens a new and exciting way for us to work on innovative treatment approaches that could one day help patients."

For decades, researchers have known that the brain controls the diameter of the peripheral arteries via the nervous system. Electrical impulses from the brain travel to the arteries via a network of nerves known as the sympathetic nervous system. This system is essential for daily life, but is often chronically over active in patients with high blood pressure or heart failure. In fact, many drugs that help with hypertension and heart failure work by decreasing the activity of the sympathetic nervous system.

However, these drugs often have serious side effects, such as fatigue, dizziness, depression and erectile dysfunction. "These drawbacks have led to the search for novel ways to inhibit sympathetic nerve action while causing fewer problems for patients," says Dr. Frans Leenen, Director of Hypertension at the Ottawa Heart Institute, and a principal author of the study.

Working with an animal model of hypertension, Dr. Leenen in collaboration with Dr. Hamlyn and Dr. Mordecai Blaustein, professor of physiology and medicine at the UM SOM, found a new link between the brain and increased blood pressure, namely, a little-known steroid called ouabain (pronounced WAH-bane). This new study is the first to identify a particular pathway by which the brain regulates the diameter of the arteries via ouabain in the bloodstream, and causes an increase in contractile proteins in the arteries. This new humoral "chronic" pathway acts together with the more "acute" sympathetic nervous system pathway to control the function of arteries and thereby contributes to e.g. high blood pressure.

"Now that we understand the role of ouabain, we can begin working on how to modify this new pathway to help people with cardiovascular problems," said Dr. Blaustein. "The potential for this is big." Dr. Blaustein, who has been doing research on the substance since 1977, said medications that block ouabain's effects might improve the lives of people with hypertension and heart failure.

The research was funded by the Canadian Institutes of Health Research, the National Institutes of Health, and the University of Maryland School of Medicine.

About the University of Ottawa Heart Institute

The University of Ottawa Heart Institute (UOHI) is Canada's largest and foremost heart health centre dedicated to understanding, treating and preventing heart disease. UOHI delivers high-tech care with a personal touch, shapes the way cardiovascular medicine is practised and revolutionizes cardiac treatment and understanding. It builds knowledge through research and translates discoveries into advanced care. UOHI serves the local, national and international community and is pioneering a new era in heart health. https://www.ottawaheart.ca

About the University of Maryland School of Medicine

The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States and continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland's Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 30 countries around the world. https://medschool.umaryland.edu/