High blood glucose increases blood vessel contraction

Scientists have shown that blood vessels contract more strongly at raised glucose levels than at normal physiological levels, which can worsen outcomes following a heart attack, according to a study published online January 6, 2016 in British Journal of Pharmacology.

The researchers also reported for the first time a novel therapeutic route to counter this effect and improve outcomes following a heart attack or stroke.

“In the experimental models we used in this study, including human blood vessels, increasing glucose to the levels that could be reached after a large meal altered vascular contraction,” said lead investigator Richard Rainbow, PhD, Lecturer in Cardiovascular Cell Physiologyat the University of Leicester, in Leicester, UK.

“This is the first study to show direct evidence of blood vessel contraction to glucose, and the potential mechanism behind this contractile response,” Dr. Rainbow added.

Previous studies by Dr. Rainbow’s team and by others have shown that glucose inhibits the voltage-gated potassium channel current in smooth muscle cells, which leads to vascular contraction.

“Our studies show that glucose has an important physiological effect on the normal functioning of the cardiovascular system,” Dr. Rainbow said. “Increases in blood sugar to pathophysiological levels cause marked changes in normal blood vessel and cardiac muscle behavior that could be life-threatening if left untreated.”

He explained: “A large number of people who suffer a heart attack will have high glucose due to the stress response. This means that even people who are not diabetic may become hyperglycemic during a heart attack.”

In this study, the researchers analyzed electrophysiologic data in the hearts of rats, pigs, and humans. When the investigators raised the level of blood glucose, they found that protein kinase C mediators inhibited voltage-gated potassium channels, causing the blood vessels to contract. Conversely, when they blocked the protein kinase C mediators, the vessels' smooth muscle cells functioned normally.

“We have identified a known signaling protein family, protein kinase C, is a key part of this enhanced contractile response, and have also shown in our experiments that we can restore the normal level of contractile response, and reverse the effects on the heart, with inhibitors of these proteins,” Dr. Rainbow said.

Targeting the specific types of protein kinase C involved in this response provides a novel therapeutic route for improving outcomes in ischemic diseases such as heart attack or stroke. This offers the potential for improved treatment for patients whose recovery from heart attack is complicated by raised levels of glucose, the researchers concluded.