Postpartum assessment of the renin angiotensin system in women with previous severe, early-onset preeclampsia.
Hladunewich MA., Kingdom J., Odutayo A., Burns K., Lai V., O'Brien T., Gandhi S., Zimpelmann J., Kiss A., Miller J., Cherney D.
CONTEXT: Women with a history of severe preeclampsia are at an increased risk for the development of vascular disease. OBJECTIVE: We hypothesized that abnormalities in the renin-angiotensin system (RAS) may be a predisposing factor. DESIGN AND SETTING: Physiological assessments were conducted at an academic center. PARTICIPANTS: Sixteen women with previous severe preeclampsia (PPE) were compared with nine previously pregnant controls (PPC) and 11 never-pregnant controls (NPC). INTERVENTIONS: Baseline circulating components of the RAS and expression of angiotensin (ANG) II type I (AT1) and type II (AT2) receptors in the skin were assessed along with the response to simulated orthostatic stress using incremental lower-body negative pressure (LBNP: -15, -25, and -40 mm Hg) and a graded ANG II infusion (1 and 3 ng/kg · min). MAIN OUTCOME MEASURES: Response to LBNP and ANG II was evaluated. RESULTS: RAS components were not different between previously pregnant groups, but were decreased compared with NPC subjects. In response to LBNP, there were significant increases in RAS components in all three groups, but the response to this stimulus was significantly lower and delayed in PPE subjects. Despite the blunted rise in circulating RAS mediators in PPE subjects, their blood pressure was maintained in 88% compared with only 33 and 55% in the PPC and NPC groups, respectively (P = 0.014). All three groups responded to the graded ANG II infusion with an increase in blood pressure that was significantly more pronounced in PPE subjects (P = 0.037) correlating with AT1/AT2 receptor expression. CONCLUSIONS: Alterations in the RAS in formerly preeclamptic patients may contribute to future vascular disease.