Scientists from King’s College London describe a new molecular mechanism for blood pressure control, an oxidant-induced vasorelaxation:
Protein kinase G (PKG) is an important protein in all tissues, but in the cardiovascular system it plays a fundamental role in blood pressure regulation. A lot is known about how this protein regulates blood pressure (as well as other important cardiac functions) and nitric oxide produced within blood vessels is known to be crucial in this process.
Now a team in King’s Cardiovascular Division has found a novel way in which the protein PKG can be regulated independently of nitric oxide. The researchers looked at the activity of oxidants such as hydrogen peroxide, which are produced in most cells of the body, on the enzyme PKG1alpha. They discovered that the oxidants cause a bond to form between two amino acids which activates PKG and this leads to a lowering of blood pressure.
Joseph Burgoyne, a King’s PhD student (funded by the British Heart Foundation) who carried out much of the laboratory work, says: ‘It’s long been suspected that there is another mechanism for lowering blood pressure which doesn’t involve nitric oxide or reactive lipids. To identify this new pathway is very exciting.’
In addition to highlighting a novel regulatory mechanism for blood pressure, the research offers new insight into the role of oxidants in the body. Free radicals and oxidants, such as hydrogen peroxide, are currently viewed as harmful, causing injury and disease. This research suggests that oxidants may have specific benefits e.g. controlling important cellular processes. It could also help to explain why antioxidant trials against heart disease have, on the whole, been unsuccessful.
Dr Philip Eaton, who led the team in King’s Cardiovascular Division, comments: ‘The research could lead to the development of drugs which activate this new pathway. These drugs might also complement a number of established therapies which work via the nitric oxide pathway.
‘Apart from its impact on blood pressure control, we now plan to explore the role of this new way of activating this protein in the setting of cardiovascular disease, including the events leading to a heart attack.’