Scientists have discovered a mechanism which raises blood pressure in pre-eclampsia, a potentially deadly condition that can occur in pregnancy, and say their work may help the search for new hypertension drugs.
Researchers at Britain's Cambridge and Nottingham Universities said they had deciphered the first step in the main process that controls blood pressure - the release of a hormone called angiotensin, from its source protein, angiotensinogen.
"Although we primarily focused on pre-eclampsia, the research also opens new leads for future research into the causes of hypertension in general," said Aiwu Zhou of Cambridge University, whose work was published in the journal Nature.
Experts estimate that the cost of treating pregnant women with pre-eclampsia is $45 billion a year in the United States, Europe, Asia, Australia and New Zealand. In developing countries, an estimated 75,000 women die of it each year.
If mothers and their babies survive, the women later have a higher risk of high blood pressure, heart disease, stroke and diabetes. The babies are often born prematurely and can suffer complications later in life.
Hypertension itself ranks as the World Health Organisation's biggest risk factor for causes of death worldwide.
Drugs currently used to treat high blood pressure include ACE inhibitors, which block the production of angiotensin, or angiotensin receptor blockers (ARBs), which stop angiotensin from taking effect in the body once it is released.
Not for pregnant women
Robin Carrell, who led the 20-year research project, said these kinds of drugs generally work well in treating standard hypertension, but they cannot be given to pregnant women as they pose a risk to the developing baby.
For their study, the scientists used an intense X-ray beam to analyse the structure of angiotensinogen and found that it can be oxidised and change shape to allow in an enzyme called renin. Renin then interacts with the protein to release the hormone angiotensin, which in turn raises blood pressure.
Researchers from Nottingham took these laboratory findings into tests on blood samples from women with pre-eclampsia and people with normal blood pressure and found that the amount of oxidised, and hence more active, angiotensinogen was higher in women with pre-eclampsia.
Carrel said that knowing how this first step worked helped explain why high blood pressure sometimes occurs in pregnancy, when the body readjusts for the oxygen needs of the foetus.
The global market for anti-hypertensives, which was around $35 billion in 2009, is dominated by generic drugs, but one of the biggest-selling brands is Novartis' Diovan. The Swiss drug firm also makes Tekturna, one of a new class of drugs that works by directly blocking renin. (Reuters Health/ October 2010)