Treating hypertensive rats with the broad-acting anti-inflammatory drug pentosan polysulfate preserves the kidney's ability to regulate pressure placed on tiny filters called glomeruli, they report in the May issue of American Journal of Physiology – Renal Physiology. A million of these fragile structures are responsible for filtering the body's total plasma volume 60 times daily.
Therapeutic intervention is a long-term goal, said Dr. Edward W. Inscho, corresponding author and physiologist in the MCG Schools of Graduate Studies and Medicine "Because the job is big, the kidneys are vulnerable to injury. If we can keep them functioning longer, quality of life is going to be better longer."
But he notes that this exact approach isn't a treatment option primarily because of side effects that can result from long-term use of anti-inflammatory drugs.
Hypertension and diabetes take a similar toll on kidneys and together, the pervasive conditions are creating a rapidly growing number of patients in kidney failure. "The number of people going to dialysis because of these two maladies just grows exponentially so there is a really good reason to figure this out," said Inscho, who recently received a $1.8 million, five-year grant from the National Heart, Lung and Blood Institute to help do just that.
In a rather vicious circle, kidneys are hurt by and contribute to hypertension; which comes first remains unresolved. But one key way hypertension hurts kidneys is by blunting the function of afferent arterioles, tiny blood vessels that feed the filtering units.
Much like a dam operator controls water flow into a river, a mechanosensor, likely located inside the smooth muscle cells that form the blood vessel walls, keeps tabs on the pressure of the blood flowing through the afferent arteriolar into the filters. If pressure gets too high, it prompts the small vessel to contract.
"You want the vasculature to constrict because filters are very delicate and the kidneys want to keep blood flow and filtration relatively constant," said Inscho noting that this balancing act enables kidney tubules, which reabsorb good things like glucose and amino acids, to do their job.
His animal studies have shown that mechanosensor function falters after just three days of high blood pressure. "The blood vessel does not seem to recognize the blood pressure increase," Inscho said. Even slightly elevated pressures resulting from too much salt consumption can render them less responsive but, at least initially, not lost. Rather the vessel's ability to sense and respond to pressure seems inactivated: when Inscho applies a vasoconstrictor agent directly onto the afferent arteriole, for example, it contracts. In the face of regular anti-inflammatory therapy, he's finding it retains the ability to sense pressure change and respond appropriately.
Inscho's new grant will help sort through just how the kidneys autoregulate pressure in normal scenarios, such as the typical blood pressure fluctuations that occur in healthy people throughout the day.
He also wants to study the role the inflammatory factors TGF-â and MCP-1 play in arteriole dysregulation. Both factors are elevated in high blood pressure and implicated in other types of vascular injury. Preliminary evidence suggests a strong link; that the factors set up some sort of signaling event that turns mechanosensors off or at least down. Ironically, impaired autoregulation leads to increased production of the inflammatory factors.
"We have data that argue that TGF-â can definitely cause these blood vessels to fail," Inscho said. "If you apply the cytokine to a healthy kidney, the blood vessel will not respond correctly; wash it off and it does. Now we also have data that if we protect the kidneys from MCP-1, we can improve the function of these vessels."
He's looking at the impact of anti-inflammatory drugs pentosan polysulfate as well as mycophenolate mofetil because of existing evidence that their use reduces protein excretion in the urine, a sign of kidney damage. Rather than as a potential therapy, he views the drugs as tools for helping dissect a complex process.
"Hypertension-related kidney damage is multifaceted, but part of that cascade of progression to injury is functional impairment of that blood vessel. We have established that, I think, unequivocally," Inscho said.
"The grant will enable us to get more information about normal function and pathology all at the same time."
Toni Baker | EurekAlert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering