It's time to expand the models for blood pressure regulation, according
to clinical pharmacologist Jens Titze, Michael. D. Titze and his fellow
workers have identified a new cast of cells and compounds that function
in the skin to regulate sodium balance and blood pressure.
"Hypertension research has traditionally focused on the kidney, blood vessels and brain, inch said Titze, associate mentor of Medicine at Vanderbilt University. "But despite massive research efforts, we still don't realize in more than 90 percent in our patients why their blood pressure is elevated. We thought a different approach might be useful. inch
L-Carnitine suppliers In a series of studies, Titze and his fellow workers found evidence that another organ system -- the skin -- was important for blood pressure control. They learned that the body stores sodium in the skin and that immune system cells and lymph capillaries (wrecks of the lymphatic system) regulate sodium balance and blood pressure. But their work has been suspect.
"I've had the impression that not many scientists or physicians really believed it -- or that it was neglected because this area of research was so not the same as conventional wisdom, inch Titze said.
Now, in findings published August 3 in the Journal of Clinical Investigation, the researchers use ancestral and molecular approaches in these animals to demonstrate that salt metabolism in the skin is important for systemic blood pressure control.
In these animals given a high-salt diet, large amounts of salt accumulate in the skin. Immune system cells (mononuclear phagocyte system, MPS) sense the sodium deposition and activate a protein called TONEBP. This protein increases expression of the growth factor VEGFC in immune cells, which builds cutaneous lymph vessel capacity and enhances sodium and chloride clearance.
The current study ensures that elimination of the TONEBP gene in MPS cells avoided the VEGFC respond to a high-salt diet and increased blood pressure. Likewise, blocking signaling through the lymph vessel VEGFC receptor inhibited the changes in lymph vessel solidity and resulted in salt-sensitive hypertension.
The findings support the idea that the immune and lymphatic systems in the skin work together to manage electrolyte (sodium, chloride) arrangement and blood pressure. Flaws in this regulatory system may be associated with salt-sensitive hypertension, Titze said.
To study the clinical importance of sodium storage in humans, the researchers implemented special over unity magnetic resonance imaging (MRI) technologies to detect sodium. They reported earlier this year that sodium is stored in muscle and skin in human beings, and that sodium storage increases with age and is associated with hypertension.
Next, they will explore what the sodium storage means -- for example, does it impact a person's risk for heart problems. They want to follow 2000 individuals for five years, measuring tissue sodium twice a year and assessing whether those that have elevated tissue sodium may have heart attacks, strokes or other artery disease.
"If sodium storage is a disease, then we will need to focus on preventing sodium storage in tissue, on assisting sodium removal from tissue, or on both, inch Titze said.
The researchers will also study whether change in lifestyle or procedures influence sodium storage and blood pressure. And they'll continue to explore the immune/lymphatic regulatory system in the skin -- and in other organ systems. Titze said that their findings claim that immune system cells work as physical regulators of metabolism.
"Perhaps there is an additional family of immune function -- homeostatic immune function -- which ensures normal electrolyte or metabolite levels and is as important as immune cell-driven defense against pathogens, inch he said.
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"Hypertension research has traditionally focused on the kidney, blood vessels and brain, inch said Titze, associate mentor of Medicine at Vanderbilt University. "But despite massive research efforts, we still don't realize in more than 90 percent in our patients why their blood pressure is elevated. We thought a different approach might be useful. inch
L-Carnitine suppliers In a series of studies, Titze and his fellow workers found evidence that another organ system -- the skin -- was important for blood pressure control. They learned that the body stores sodium in the skin and that immune system cells and lymph capillaries (wrecks of the lymphatic system) regulate sodium balance and blood pressure. But their work has been suspect.
"I've had the impression that not many scientists or physicians really believed it -- or that it was neglected because this area of research was so not the same as conventional wisdom, inch Titze said.
Now, in findings published August 3 in the Journal of Clinical Investigation, the researchers use ancestral and molecular approaches in these animals to demonstrate that salt metabolism in the skin is important for systemic blood pressure control.
In these animals given a high-salt diet, large amounts of salt accumulate in the skin. Immune system cells (mononuclear phagocyte system, MPS) sense the sodium deposition and activate a protein called TONEBP. This protein increases expression of the growth factor VEGFC in immune cells, which builds cutaneous lymph vessel capacity and enhances sodium and chloride clearance.
The current study ensures that elimination of the TONEBP gene in MPS cells avoided the VEGFC respond to a high-salt diet and increased blood pressure. Likewise, blocking signaling through the lymph vessel VEGFC receptor inhibited the changes in lymph vessel solidity and resulted in salt-sensitive hypertension.
The findings support the idea that the immune and lymphatic systems in the skin work together to manage electrolyte (sodium, chloride) arrangement and blood pressure. Flaws in this regulatory system may be associated with salt-sensitive hypertension, Titze said.
To study the clinical importance of sodium storage in humans, the researchers implemented special over unity magnetic resonance imaging (MRI) technologies to detect sodium. They reported earlier this year that sodium is stored in muscle and skin in human beings, and that sodium storage increases with age and is associated with hypertension.
Next, they will explore what the sodium storage means -- for example, does it impact a person's risk for heart problems. They want to follow 2000 individuals for five years, measuring tissue sodium twice a year and assessing whether those that have elevated tissue sodium may have heart attacks, strokes or other artery disease.
"If sodium storage is a disease, then we will need to focus on preventing sodium storage in tissue, on assisting sodium removal from tissue, or on both, inch Titze said.
The researchers will also study whether change in lifestyle or procedures influence sodium storage and blood pressure. And they'll continue to explore the immune/lymphatic regulatory system in the skin -- and in other organ systems. Titze said that their findings claim that immune system cells work as physical regulators of metabolism.
"Perhaps there is an additional family of immune function -- homeostatic immune function -- which ensures normal electrolyte or metabolite levels and is as important as immune cell-driven defense against pathogens, inch he said.
Learn more:
Monosodium Glutamate exporters
Sucralose suppliers
Genetic clue to irritable bowel syndrome found