Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression

The balance between proangiogenic and antiangiogenic factors, such as vascular endothelial growth factor, placental growth factor, and soluble fms like tyrosine kinase-1 (sFlt-1), is altered in preeclampsia, and this dysregulation of angiogenic factors may be important in the pathogenesis of preeclampsia. Although sFlt-1 is elevated in preeclampsia, the mechanisms responsible for increasing this antiangiogenic factor remain unclear. We hypothesized that the hypertension produced by reduced uterine perfusion pressure (RUPP) is associated with increased sFlt-1 expression and decreased plasma vascular endothelial growth factor and placental growth factor concentrations in the pregnant rat. Arterial pressure was increased (130 +/- 3 versus 100 +/- 2 mm Hg; P < 0.01) in the RUPP rats compared with the normal pregnant control rats. Plasma sFlt- 1 concentration (660 +/- 270 versus 82 +/- 26 pg/ mL; P < 0.05) was increased, whereas plasma free placental growth factor (0.28 +/- 0.05 versus 1.7 +/- 0.5 pg/ mL; P < 0.01) and vascular endothelial growth factor (594 +/- 34 versus 830 +/- 33 pg/ mL; P < 0.01) concentrations were decreased in the RUPP rats compared with normal pregnant rats. Plasma sFlt- 1: placental growth factor (37.2 +/- 7.8 versus 8.9 +/- 1.6; P < 0.02) and sFlt-1: vascular endothelial growth factor (0.86 +/- 0.22 versus 0.28 +/- 0.06; P < 0.05) ratios were increased in the RUPP rats compared with normal pregnant rats. Immunoreactive placental sFlt-1 was increased (1.1 +/- 0.1 versus 0.3 +/- 0.1; P < 0.01) in RUPP rats contrasted with the normal pregnant rats. These findings support our hypothesis that RUPP increases the expression of sFlt-1 and alters the balance of angiogenic factors in the maternal circulation. These data also indicate that the RUPP model of pregnancy-induced hypertension may provide an invaluable model for mechanistic studies into the role of sFlt-1 in the pathogenesis preeclampsia. (Hypertension. 2007; 50: 1142- 1147.).