Writing in the journal Circulation, the research team identify resveratrol’s ability to induce protein oxidation as an unexpected finding in mice that supports its observed effects on blood pressure.
“We’re slowly realising that oxidants aren’t always the villain,” said study lead author Dr Joseph Burgoyne, senior lecturer within the cardiovascular sciences section at Kings College, London.
“Our research shows that a molecule once deemed an antioxidant exerts its beneficial effects through oxidation. We think that many other so-called ‘antioxidants’ might also work in this way.
“Our work could lay the foundations for chemically altering resveratrol to improve its delivery to the body, or designing new, more potent drugs which use the same pathway. In the future, we could have a whole new class of blood pressure drugs.”
However, reaction to the study was muted, with fellow researchers critical of the dosage used in the study and the challenges of applying its findings to human subjects.
“The dose here of 320 milligrams per kilogram (mg/kg) in mice can be considered equal to treating a human with 15 to 20 grams (g) resveratrol,” said professor Roger Corder, emeritus professor of experimental therapeutics at Queen Mary University of London and author of ‘The Wine Diet.’
“This amount is ridiculous and in red wine terms equivalent to more than 3000 litres of wine. There’s no attempt to show the threshold dose of resveratrol for effects on blood pressure. It could be as little as 5 mg/kg.
“Experimentally the lowest dose that reduces blood pressure should have been found and then the researchers should have carried out experiments using that dose to provide insights into the mechanism. Is this mechanism important? Based on the data presented it is difficult to reach any satisfactory conclusions.”
In this study, British Heart Foundation-funded scientists from the University administered a dose of resveratrol to mice with induced high blood pressure. This caused the blood vessels of the mice to relax and blood pressure to drop.
The team also demonstrated that through in vitro experiments, mass spectrometry and electron paramagnetic resonance the mechanism of action of this polyphenol could be determined.
These techniques also played a central role in proving that resveratrol works in the same way in smooth muscle cells extracted from human blood vessels.
“The real value of this study is in revealing the surprising way in which resveratrol exerts its effects, and with it the possibility of new blood pressure drugs which work in a similar way,” said Metin Avkiran, King’s professor of molecular cardiology and associate medical director at the British Heart Foundation.
“Although you can buy resveratrol supplements, the best way to keep your blood pressure under control is through a healthy lifestyle, a balanced diet and taking any medicines prescribed by your doctor.”
Limitations for future consideration
The study acknowledged the limitations of this study with the lack of patient data, which would support the possibility of these animal findings translating to humans.
“Based on our findings we predict that under disease conditions with altered reactive oxygen species (ROS) bioavailability and/or pH, the ability of resveratrol to induce protein oxidation may be enhanced, thus potentiating beneficial signalling,” the study said.
Dr Bob Patton, alcohol researcher and lecturer in clinical psychology at the University of Surrey, said, “These scientists have demonstrated that under laboratory conditions, and using a very high dosage, that resveratrol can significantly lower blood pressure in mice.
“The authors are quick to point out that this effect has not been tested in human studies. To match the effective dosage in the study, you would need to drink about 1000 bottles of wine, which is of course impossible.”
Published online: doi.org/10.1161/CIRCULATIONAHA.118.037398
“Blood pressure-lowering by the antioxidant resveratrol is counterintuitively mediated by oxidation of cGMP-dependent protein kinase.”
Authors: Prysyazhna et al.