MDC researchers and clinicians identify mediator of blood pressure regulation in the liver

For 60 years, scientists have puzzled over the possibility of a hepatic osmoreceptor that influences blood pressure regulation. Now, researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, the Experimental and Clinical Research Center (ECRC) of the MDC and Charité and the Hannover Medical School (MHH) appear to have made a breakthrough discovery. Dr. Stefan Lechner and Professor Gary R. Lewin (both of MDC), Professor Friedrich C. Luft (ECRC) and Professor Jens Jordan (ECRC; now MHH) have discovered a new group of sensory neurons in the mouse liver which mediates the regulation of blood pressure and metabolism. This peripheral control center outside of the brain is triggered simply by drinking water and leads to an elevation of blood pressure in sick and elderly people. (Neuron, No. 69 (2) pp. 332-344)*

More than ten years ago Professor Jens Jordan, MD, then a research fellow at Vanderbilt University in Nashville, Tennessee, observed a phenomenon together with his colleagues, more or less by accident. Later, at the former Franz Volhard Clinic of the Charité in Berlin-Buch, Jens Jordan again observed that in patients with a damaged nervous system, blood pressure readings rose by as much as 50 mm Hg if the patients drank a half liter of water all at once. "In young people whose sympathetic nervous system was stimulated by drugs, water intake also caused blood pressure levels to rise," said Professor Friedrich C. Luft of the ECRC. "Even in healthy older people, water drinking triggers a regulator for blood pressure." The two clinicians invited neuroscientists at MDC to collaborate with them and started a joint research project.

For 60 years researchers have suspected that there must also be a control center for the body's self-regulation located outside of the brain. Motivated by findings of recent studies, the researchers in Berlin-Buch therefore looked for sensory neurons specifically in organs peripheral to the central nervous system that would detect body changes caused by water intake and would thus be able to activate a regulator which in old and sick people causes blood pressure to rise and which stimulates metabolism in healthy young people.

"In this entire process, osmolality plays a key role," explained Dr. Stefan Lechner, a member of Professor Lewin's research group. "It is the measure of the body's water balance. And it indicates how many molecules are dissolved in a liter of fluid. Each species has a characteristic set point for osmolality, which depends to a great extent on the immediate living conditions. We wanted to know how deviations of osmolality are able to activate a regulator."

The researchers observed in the mouse model that specific neurons in the liver react actively to water intake. The water the mice drink is absorbed in the small intestine and reaches the blood system via the liver. Due to the sudden water intake, the osmolality in the blood vessels of the liver falls under its set-point value. This deviation is registered by sensory neurons in the liver, the so-called osmoreceptors, as the researchers could now demonstrate. They found that the osmoreceptors transform the information into an electrical signal, which in turn triggers a reflex and stimulates the hepatic blood vessels to raise blood pressure.