A new mouse strain in which pregnant females develop high blood pressure may help scientists understand--and perhaps treat--a sometimes fatal condition in pregnant women, says a Report in the 8 November issue of Science.
In the last trimester of pregnancy, an expectant mother's blood pressure can rocket out of control, damaging her kidney, liver, and heart, and putting both her life and that of the child she is carrying at risk. No one knows what causes pregnancy-induced hypertension (PIH) or an almost identical condition called preeclampsia, which affect up to 10% of human pregnancies and cause the majority of pregnancy-related complications. And efforts to study the condition, as well as to develop therapies for it, have been handicapped by lack of an animal model that reproduces the pathological features of PIH.
New work by Akiyoshi Fukamizu and his colleagues at the University of Tsukuba, Japan, may change that. His team bred mice they had genetically altered to carry one of two genes that encode proteins involved in blood pressure control. One gene makes a precursor of angiotensin II, a potent protein that raises blood pressure. The other makes renin, the enzyme that cleaves angiotensin II from the precursor. When the right mating combination brought these two proteins together in pregnant females, they developed high blood pressure and other changes reminiscent of PIH.
``It's probably some of the most innovative work I have seen in a long time in this field,'' says Charles Rosenfeld, a neonatologist at the University of Texas Southwestern Medical School in Dallas. He and other PIH researchers think the mouse model may shed light on the mechanisms by which high blood pressure wreaks havoc on both mother and fetus. Ultimately, such an understanding might lead to better therapies for PIH, which currently can only be cured by inducing a premature delivery.
The big question now is whether the mouse model does, in fact, reflect what's happening in human PIH. One thing giving pause to some scientists is puzzling features in the PIH mice, including the fact that the hypertension does not develop if females overexpressing human renin are mated with males that overproduce the human angiotensin II precursor. ``This is not the perfect model," Rosenfeld says, "but it can give us some insights.''