Studying the brain could help us to better understand, and control, high blood pressure. June Davison talks exclusively to Professor Julian Paton about his BHF-funded research.
For every three people who read this article, one of them will have high blood pressure (hypertension). While there's an armoury of drugs available to treat hypertension, nearly half of those who are prescribed medication for it still suffer from the condition. People with hypertension are at a higher risk of heart attack, strokeand kidney disease.
A team led by Professor Julian Paton and his co-principal investigator Professor Sergey Kasparov is researching possible causes of hypertension. The Bristol-based team hopes that its research will inform the development of future treatments to help those who don’t respond to current
medication.
medication.
“Some of the patients in our clinic are on as many as six or more tablets a day, and still have dangerously high blood pressure,” says Professor Paton. “So, there is huge justification for why we need to do more research into high blood pressure and find better ways of treating it.”There is huge justification for why we need to do more research into high blood pressure and find better ways of treating it
Brain power
The focus of Professor Paton’s research is on the relationship between high blood pressure and the brain, specifically the areas called the hypothalamus and the brainstem. These older parts of the brain house different groups of neurons (nerve cells) that transmit messages via the autonomic nervous system, which controls blood pressure. “We don’t control them consciously; they’re controlled automatically,” explains the professor.
Most blood vessels throughout your body are ‘innervated’ or touched by these autonomic or sympathetic nerve cells. The activity of sympathetic nerve cells causes vessels to constrict, which generates our blood pressure. Blood pressure is necessary for blood to flow around the body, making sure your organs receive oxygen and nutrients. Some sympathetic nerve cells travel to cardiovascular ‘target organs’ such as your heart and kidneys. “These are important organs that also help to control blood pressure,” he says.
In stressful situations, our bodies can go into a state of what the professor calls ‘fight or flight’. This is when the sympathetic nervous system becomes hyperactive, causing our blood pressure to rise briefly.
This is completely normal as it’s our body’s way of priming us to either fight or flee from danger;
higher blood pressure means more blood flow, which in turn supplies the additional oxygen and nutrients our muscles need.
higher blood pressure means more blood flow, which in turn supplies the additional oxygen and nutrients our muscles need.
Critically, Professor Paton’s team believes that, as well as signals travelling from the brain to the blood vessels, most organs can send information back to the brain.
“For example, if you have a narrowing of the renal artery (the artery that supplies blood to the kidney) and the kidney isn’t getting enough blood, the kidney starts ‘screaming’ signals at the brain to increase blood pressure. As a consequence, this increases blood flow to the kidney, but you become hypertensive,” he explains. “And we believe that the brain responds in a similar way.”
The researcher: Julian Paton
Julian Paton is Professorial Research Fellow in Physiology at the University of Bristol.
Professor Paton describes himself as “half neuroscientist, half cardiovascular scientist”. For many years, he’s been involved in looking at how the brain controls blood pressure.
“I grew up on a farm and was always intrigued with farm machinery and how it worked,” he says. “Out of that curiosity came an interest in physiology, which is basically body mechanics. It’s about understanding how the body functions, and why it stops working properly. I find the mechanisms involved in the maintenance of blood pressure fascinating, and we know less about the brain than any other organ, so it’s a challenge. But, then, I am always up for a tough challenge.”
Professor Paton has been funded by the BHF since his PhD was awarded in 1987, for which he is most grateful.
Selfish brain syndrome
The BHF has awarded a £980,415 research grant to Professor Paton, which will further his research into what he describes as the “selfish brain hypothesis of hypertension”.
Essentially, this new theory says that when the blood flow to the brain is reduced, the brain activates the sympathetic nervous system to send out messages to constrict blood vessels around the body. This increases blood pressure, which provides the brain with more blood. While we need some constriction to maintain a healthy blood pressure, it’s the over-activity of the brain (the most selfish organ) that causes too much constriction, which results in raised blood pressure.
“We already know that when someone has high blood pressure, the nerve fibres that innervate the blood vessels are much more active,” explains the professor.
In many patients with hypertension, the vessels at the base of the brain are narrowed and have high resistance (or a low blood flow). Professor Paton’s team is interested in what causes this high resistance because, if they can figure that out, theoretically they could reduce the restriction. This means the brain would no longer feel the need to send out an SOS for additional blood flow, and there would be no increase in blood pressure.We want to see if we can reverse the issue of poor blood flow into the brain in the hope that this will cause a reduction in the blood pressure
“We want to understand more about why these vessels constrict, become stiff and why their walls thicken. All these things contribute to the resistance and starve the brain of blood,” says the professor. “We want to see if we can reverse the issue of poor blood flow into the brain in the hope that this will cause a reduction in the blood pressure.”
The chicken or the egg?
Key to Professor Paton’s research is to find out which comes first: is reduced blood flow to the brain a consequence of hypertension or is it a decrease in brain blood flow that triggers the hypertension?
He firmly believes it is the latter but, as he says, “We’re putting the dogma on its head, which is pretty provocative.
“Our first step is to confirm that if resistance to brain blood flow is increased, it definitely causes hypertension. We then need to work out what the triggers are within the brain that relay the ‘poor brain blood flow’ signal into increased sympathetic activity and high blood pressure. Once we’ve done this, we can start looking at targeting those triggers, which will hopefully result in a reduction of blood pressure.”
Mapping the mind
The team is using the latest cutting-edge techniques, including radio-telemetry (a means of recording blood pressure remotely and continuously) and fMRI (functional magnetic resonance imaging), to visualise the brain and its blood vessels, while at the same time record changes in blood flow. Professor Paton’s team is also working to identify and manipulate the genes that control brain blood flow.
The professor is optimistic about what the future holds. “We hope to see some initial results within 18 months and, if we make some exciting discoveries, we could think about testing patients with new medications or stenting vertebral arteries hopefully within the next five to seven years,” he says.
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