Discovery could open new doors in blood pressure research
The Internal Medicine Research Group at the University of Oulu, Finland, has discovered a previously unknown blood pressure regulation circuit. This discovery is particularly linked to high blood pressure due to overweight and obesity, and will open new doors in the field of blood pressure research.
Image credit: University of Oulu
The study focused on a nuclear receptor that senses the chemical environment of cells, the pregnane X receptor (PXR), which is a key regulator of drug metabolism in the liver.
In a recent paper, researchers show how PXR increases blood pressure in humans and rats when activated. Regulated by PXR activation, the liver produces 4beta-hydroxycholesterol (4bHC) and its increasing concentration is linked to a drop in blood pressure.
“This is a chain of effects in which 4bHC appears to counteract PXR activation,” explains Janne Hukkanen, professor of internal medicine, who was the lead researcher.
The study showed that healthy subjects with the lowest blood pressure had the highest levels of 4bHC. Additionally, it was noted that 4bHC levels in overweight and obese subjects were significantly lower than in normal weight subjects. This may at least partly explain the high blood pressure common in obese people.
It is common knowledge that hypertension is more common in overweight and obese people than in the normal weight population, but the underlying mechanism has not been fully established. This discovery improves our understanding of high blood pressure caused by excess weight and obesity.
Janne Hukkanen, Professor of Internal Medicine
Hypertension increases the risk of many cardiovascular events, such as strokes and heart attacks. Therefore, high blood pressure is the single most important risk factor in reducing years of healthy life worldwide.
The discovery of a new circuit for regulating blood pressure could also allow the development of antihypertensive drugs that work in a completely new way. “For example, overweight and obese people could be offered more effective drugs and better targeted treatment,” Hukkanen said.
PXR has been the subject of active research in recent years. The research group previously established that PXR activation causes an increase in harmful LDL cholesterol in humans.
Many drugs, food ingredients, and environmental chemicals activate the PXR receptor. Receptor-activating chemicals are also found in many pesticides, flame retardants, plastic additives, and environmental pollutants.
“Our research provides strong evidence that the chemical composition of our environment may also play a role in high blood pressure,” adds Hukkanen.
The study was conducted in collaboration by internal medicine and pharmacology researchers from the University of Oulu, Admescope Ltd and the University of Eastern Finland.
The study was funded by the Finnish Foundation for Cardiovascular Research, the Finnish Medical Foundation and the Health Care Support Foundation of Northern Finland.
Rahunen, R. et al. (2022) Pregnane X Receptor‒4β‐Hydroxycholesterol Axis in the Regulation of Overweight‐ and Obesity‐Induced Hypertension. Journal of the American Heart Association. doi.org/10.1161/JAHA.121.023492.