For decades, researchers have known that the brain controls the diameter of the peripheral arteries, the vessels that carry blood to the arms, legs, hands and feet. Electrical impulses from the brain travel to these arteries through a network of nerves known as the sympathetic nervous system, adjusting blood pressure levels.
New research by scientists at the University of Ottawa Heart Institute and the University of Maryland School of Medicine (UM SOM) has uncovered a pathway by which the brain uses an unusual steroid to control blood pressure. The results, published in the journal Public Library of Science (PLOS) One, point to new approaches for treating high blood pressure and heart failure.
Control of the peripheral arteries by the sympathetic nervous system is essential for daily life, but this mechanism is often chronically overactive 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 can 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," said Frans Leenen, MD, PhD, Director of the Hypertension Clinic and Hypertension Research at the Heart Institute, and a principal author of the study.
Working with an animal model of hypertension, Dr. Leenen, in collaboration with John Hamlyn, PhD, and Mordecai Blaustein, MD, of UM SOM, has found a new link between the brain and increased blood pressure, namely, a little-known steroid called ouabain (pronounced WAH-bane). The study is the first to identify the particular pathway by which the brain regulates the diameter of arteries via ouabain in the bloodstream, causing an increase in contractile proteins in the arteries. This new "chronic" pathway acts together with the more "acute" sympathetic nervous system pathway to control the function of arteries and, thereby, contribute to high blood pressure.
"This research gives us an entirely new way of understanding how the brain and the cardiovascular system work together," said Dr. Hamlyn. "It opens a new and exciting way for us to work on innovative treatment approaches that could one day help patients."
Interestingly, the ouabain produced by mammals has a very similar molecular structure to a plant-based ouabain long known to be used by African hunters in making poison arrows. In fact, there is some controversy as to whether mammals do actually produce ouabain, a matter that this research should help to resolve.
Dr. Blaustein, who has been studying the substance since 1977, said medications that block ouabain's effects could improve the lives of people with hypertension and heart failure. "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."