A description of the research, conducted in mice and test tubes, appeared online Feb. 11 in the journal Proceedings of the National Academy of Sciences.
“The contribution that gut microbes apparently make to blood pressure regulation and human health is a surprise,” says Jennifer Pluznick, Ph.D., assistant professor of physiology at the Johns Hopkins University School of Medicine. “There is still much to learn about this mechanism, but we now know some of the players and how they interact,” she adds.
Pluznick says that several years ago, thanks to a “happy coincidence,” she found — in the kidney — some of the same odor-sensing proteins that give the nose its powers. Focusing on one of those proteins, olfactory receptor 78 (Olfr78), her team specifically located it in the major branches of the kidney’s artery and in the smaller arterioles that lead into the kidney’s filtering structures. Olfr78 also turned up in the walls of small blood vessels throughout the body, she says, particularly in the heart, diaphragm, skeletal muscle and skin.
To figure out which molecules bind and activate Olfr78, the scientists programmed cells to have Olfr78 protein receptors on their surface. They also gave these same cells the ability to start a light-producing chemical reaction whenever Olfr78 is activated. By adding different cocktails of molecules to the cells and measuring the light the cells produced, they homed in on a single mixture that activated Olfr78. They then tested each component in that mix and found that only acetic acid (a.k.a. vinegar) bound Olfr78 and caused the reaction.
Acetic acid and its alter ego, acetate, are part of a group of molecules known as short chain fatty acids (SCFAs). When the team tested other molecules in this group, they found that propionate, which is similar to acetate, also binds Olfr78. In the body of mammals, including humans, SCFAs are made when zillions of bacteria lining the gut digest starch and cellulose from plant-based foods. The SCFAs are absorbed by the intestines into the blood stream, where they can interact with Olfr78.
To pinpoint the effect of Olfr78, the scientists gave SCFAs to mice missing the Olfr78 gene and found that the rodents’ blood pressure decreased, suggesting that SCFAs normally induce Olfr78 to elevate blood pressure. However, when they gave SCFAs to normal mice with intact Olfr78, they did not see the expected increase in blood pressure, but rather a decrease, though it was less pronounced than before.
To test the effect of reducing the SCFAs available to Olfr78, the team gave mice a three-week course of antibiotics to wipe out the gut microbes responsible for SCFA production. In this case, normal mice showed very little change in blood pressure, but mice without Olfr78 experienced an increase in blood pressure, suggesting that there were other factors involved in the Olfr78/SCFA/blood pressure relationship.
The mystery was solved, Pluznick says, when the team examined mice lacking Gpr41, a non-smell-related protein receptor located in blood vessel walls that also binds SCFAs. When SCFAs bind to Gpr41, blood pressure is decreased. The researchers eventually discovered that Olfr78 and Gpr41 both are activated by SCFAs, but with contradictory effects. The negative effect of Gpr41 is counterbalanced by the positive effect of Olfr78, but Gpr41’s effect is stronger, so an increase in SCFAs produces an overall decrease in blood pressure.
“We don’t have the full story yet,” says Pluznick. “There are many players involved in the maintenance of stable levels of blood pressure, and these are just a few of them. We don’t know why it would be beneficial for blood pressure to decrease after eating or why gut microbes would play a part in signaling that change. But our work opens the door for exploring the effects of antibiotic treatments, probiotics and other dietary changes on blood pressure levels in mice, and perhaps eventually people.”
Other authors of the report include Ryan Protzko of the Johns Hopkins University School of Medicine; Jinah Han, La-Xiang Wan, Tong Wang, Anne Eichmann and Michael Caplan of the Yale University School of Medicine; Haykanush Gevorgyan, Arnold Sipos and Janos Peti-Peterdi of the University of Southern California; and others from the College de France, Columbia University, the Washington University School of Medicine and the University of Texas Southwestern Medical Center.This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK081610, DK64324, DK17433) and the Leducq Foundation.
Catherine Kolf | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences