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In Muscat, Rare Mice Help Scientists Understand High Blood Pressure

MUSCAT—Ammar Boudaka shows a mixture of pride and embarrassment as he gives me a tour of the on-campus animal facility at Sultan Qaboos University. “I apologize for the smell, it will be quite bad,” he says, as we don our protective clothing in the reception area.

The facility—one of just a few in the Middle East—breeds a menagerie of genetically diverse mice and rats. Mice are one of the most frequently used models of human disease because, despite major differences in appearance between the two species, they are biologically very similar. Having the rodents on site allows scientists at the university to conduct an array of different medical trials. Boudaka, for example, uses rodents with high blood pressure to investigate the condition.

Studies have shown that high blood pressure is the leading cause of strokes, heart attacks and kidney failure. All these diseases are on the rise in the Arab world—additionally, heart disease caused by high blood pressure is the ninth biggest cause of death in the region, according to 2010 data from the Institute for Health Metrics and Evaluation.

As we step into the animal facility, I discover Boudaka wasn’t wrong about the smell. When he opens the door from reception to the breeding rooms, the odor wafts through. The scent is a strong mixture of animal feed, sawdust and a farmyard-like fragrance coupled with the clinic aromas of cleaning fluid.

But as we progress from room to room and Boudaka shows off the various genetic strains of mice and rats they can breed, the smell doesn’t seem to hamper his enthusiasm.

“A facility like this means we’re able to do serious research at international standards,” he says.

Rare Mice Give Insight to High Blood Pressure 

Boudaka, originally from Libya, studied for his Ph.D. at Gifu University in Japan and has been an assistant professor in the department of physiology at Sultan Qaboos University since 2012. A few years ago, with the help of former colleagues in Gifu, he was able to import some especially rare rodents from Japan that have helped him create new biological insights.

The Japanese mice were genetically altered so that their cell membranes didn’t have a receptor known as TRPV4. Boudaka used these mice to discover a new purpose for the receptor—he showed that it has a role in digesting food.

When an animal eats something, parts of the esophagus stretch as the food presses against it. The receptor responds to this pressure and sends signals to the central nervous system to begin the muscle contractions that push food through the gullet and digestive organs.

Rats in the on-campus breeding center at Sultan Qaboos University (Photo: Benjamin Plackett).

Later, Boudaka theorized that since the receptor responded to the physical pressure of food, it may also respond to blood pressure, also known as hypertension.

“I thought the receptor might be activated by higher levels of blood pressure and then start the feedback process for the body to correct it,” he explains.

His hunch turned out to be right.

In a recently published research paper, Boudaka showed that rats with spontaneously high blood pressure—that’s to say they weren’t specifically bred for hypertension—had significantly fewer TRPV4 receptors than rats with normal blood pressure. He concludes that rats with fewer TRPV4 are less able to regulate their blood pressure because they have fewer receptors to respond to it.

Will New Insight Help Treatment?

“It’s the archetypal complex disease and there are many causes—both genetic and lifestyle,” says Morris Brown, a professor of endocrine hypertension at Queen Mary University of London. “It’s always helpful to know more about it at a molecular level. Doing so can open new possibilities of treatment. However, we already have fantastic drugs that are cheap.”

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Globally, as many as 40 percent of adults older than 25 are affected by high blood pressure, according to the World Health Organization. But there is no singular biological cause of high blood pressure—Boudaka’s findings add to other known causes. For example, one study back in 2012 found that another type of cell receptor was linked to hypertension.

But it’s important to identify as many potential causes of high blood pressure as possible, says Boudaka, because with each new biological explanation for the problem comes a potential new avenue for drug developers to explore.

“My hope is that work like this could be used to develop innovative treatment options,” he says.

While Brown acknowledges research like this has that potential, he says the market for blood pressure drugs is already very competitive. “None of the major companies feel very enthusiastic about a program of new drugs because they’re unsure about how they’d compete.”

While Sultan Qaboos University’s animal facility allows its researchers to conduct sophisticated experiments and even though lab rats and mice make for good study models, it’s also not an automatic given that the results will hold true in humans.

Indeed, Boudaka’s next step would be to replicate his experiments on human tissue, as he pursues his research on a disease that is only going to become more prevalent for the region in the coming years.

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