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The control of vascular tone is multifactorial. The autonomic nervous system, intrinsic vascular smooth muscle reflexes and the endothelium all play a role in maintaining blood flow to an organ. Defects in one parameter are counterbalanced by another, making it difficult to understand the primary pathology. Prospective studies in healthy and diseased pregnancy will help our understanding of cardiovascular change during pregnancy and in those women who go on to develop pre-eclampsia.

One of the most important adaptations made by the endothelium during healthy pregnancy is increased nitric oxide synthase (NOS) activity, which is stimulated by the gestational increase in estradiol levels. During pregnancy, maternal organs vary in their degree of vasodilatation, possibly reflecting the variable expression of eNOS in their vasculature. Blood flow to the uterus in particular increases secondary to increased NOS activity. A healthy endothelium also prevents hemostasis and inflammatory activity. When the endothelium is damaged, the vasodilatory, anti-thrombotic and anti-inflammatory roles of the endothelium are attenuated. This leads to reduced maternal organ blood flow due to vasoconstriction, microthrombi and local inflammation, all of which are present in affected organs during pre-eclampsia.

The risk factors for pre-eclampsia (all except smoking) are similar to those for cardiovascular disease in later life. It is clear therefore that some women who go on to develop pre-eclampsia have pre-existing endothelial dysfunction. They are vulnerable to even a mild inflammatory stress or increased antiangiogenic response. The source of this anti-endothelial stress appears to be a poorly implanted placenta, but may also involve a hormone-induced metabolic state that is damaging to the endothelium. Further understanding of the clinical spectrum of pre-eclampsia will allow us to customize anti-pre-eclampsia prophylaxis according to maternal and possibly paternal phenotype.

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