Researchers at the University of Maryland School of Medicine (UM SOM) and the Ottawa Heart Institute report the discovery of a new pathway by which the brain uses an unusual steroid to control blood pressure. The study (“Neuroendocrine Humoral and Vascular Components in the Pressor Pathway for Brain Angiotensin II: A New Axis in Long Term Blood Pressure Control”), which also suggests new approaches for treating high blood pressure and heart failure, appears in PLOS One.

“This research gives us an entirely new way of understanding how the brain and the cardiovascular system work together,” said John Hamlyn, Ph.D., 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 the sympathetic nervous system, which is essential for daily life, but is often chronically overactive in high blood pressure and heart failure. In fact, many drugs that help with hypertension and heart failure work by decreasing both acute and chronic activity in the sympathetic nervous system.

However, these drugs often have serious side effects, such as fatigue, dizziness, and erectile dysfunction. “These drawbacks have led to the search for novel ways to inhibit the sympathetic nervous system while causing fewer problems for hypertension and heart failure patients,” says Frans Leenen, M.D., Ph.D., director of hypertension at the Ottawa Heart Institute, and a principal author of the study.

Working with an animal model of hypertension, Drs. Hamlyn and Leenen, along with Mordecai Blaustein, M.D., professor of physiology and medicine at the UM SOM, found a new link between the brain and increased blood pressure, i.e., a steroid called ouabain, which was discovered in human blood more than 20 years ago by Drs. Hamlyn and Blaustein with scientists from Upjohn.

The new study is the first to identify the particular pathway that connects the brain to ouabain's effects on proteins that regulate arterial calcium and contraction. Through this mechanism, ouabain makes arteries more sensitive to sympathetic stimulation, and as a result the enhanced artery constriction promotes chronic hypertension.

“We conclude that brain Ang [angiotensin] II activates a CNS-humoral axis involving plasma EO [ouabain],” wrote the investigators. “The elevated EO reprograms peripheral ion transport pathways known to control arterial Na+ and Ca2+ homeostasis; this increases contractility and augments sympathetic effects. The new axis likely contributes to the chronic pressor effect of brain Ang II.”

“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.”

He added that medications that block ouabain's effects might improve the lives of people with hypertension and heart failure.








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