Study reveals fine-tuning mechanism of angiotensinogen in pre-eclampsia

An exciting collaboration between the Universities of Cambridge and Nottingham has resulted in new insights into the hypertension that frequently blights pregnancy.

The results, published in the journal Nature [online 6^th October], describe the solving of the first step in the principal process that controls blood pressure — the release of the hormone angiotensin from its source protein, angiotensinogen.

Every day, millions of people are treated with drugs which either block the production of angiotensin, (ACE inhibitors), or stop it from taking effect in the body once it is released, (angiotensin receptor blockers). These drugs are crucial for reducing risks to health, by lowering blood pressure and make up nearly six per cent of all prescriptions written in the UK.

Study into the causes and, potentially, prevention of this hypertension could help to reduce the burden it places on the NHS. In the past five years, the number of prescriptions of ACE inhibitors and angiotensin receptor blockers has risen to 13.4 million.

The Cambridge findings unexpectedly revealed a fine-tuning mechanism in angiotensinogen that is responsive to changes in tissue oxygen. The Nottingham contribution has been in showing how this change — from a less active to a more active form — occurs in the human body as well as the test-tube.

Professor Fiona Broughton Pipkin of the Department of Obstetrics and Gynaecology, University of Nottingham, has been studying angiotensin in normal and pre-eclamptic pregnancy for 30 years.

Pre-eclampsia — new high blood pressure and kidney problems in pregnancy — affects about one woman in 20 in the UK during pregnancy, and often needs premature delivery. In its most serious form it is one of the two most important causes of maternal death in the UK, and worldwide kills at least 55,000 pregnant women per year. It is one of the 'oxidative stress' diseases, and probably originates in the placenta, or afterbirth.

Professor Broughton Pipkin said: "We decided that examining the ratio of the two forms of angiotensinogen in plasma from pre-eclamptic women and those with normal blood pressure would be an excellent test of the hypothesis that this mechanism could contribute to high blood pressure.

"We sent coded samples to Cambridge and were thrilled when we broke the code to find that the results fitted our prediction beautifully. They also fit with the changes in the placenta in pre-eclampsia. This is an absolutely novel approach, which is providing new insights into what goes wrong in pre-eclampsia.

"The collaboration is continuing and expanding, and we hope very much to get rapid grant funding".

Source :  Nature