Changes in Endothelial Function Precede the Clinical Disease in Women in Whom Preeclampsia Develops

Abstract

Abstract-Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Key Words: endothelium-derived factors Ⅲ hypertension Ⅲ microcirculation Ⅲ nitric oxide Ⅲ preeclampsia Ⅲ pregnancy P reeclampsia (PE) continues to be a leading cause of maternal and perinatal morbidity and mortality. Characteristic hemodynamic changes occur during normal human pregnancy, which include peripheral vasodilatation, reductions in total vascular resistance, and decreased arterial blood pressure. The precise reasons for such changes are not clear, but recent evidence points to changes in endothelial function and nitric oxide activity as contributory factors. 1,2 In PE there is accumulating evidence for a pathogenic model whereby deficient trophoblast invasion of the maternal spiral arteries leads to a poorly perfused feto-placental unit. 3 This results in secretion of a factor(s) by the placenta into the maternal circulation, which activates the vascular endothelium. 4,5 However, although endothelial dysfunction appears to be a key player in the pathophysiology of PE, there appears to be a difference in the way in which endothelial damage is expressed depending on the particular vascular bed studied. For example, arterial endothelial function, assessed using ultrasound measurements of flow-mediated dilatation, is diminished in women who have PE compared with normal pregnant women. 6 -8 Conversely in the microcirculation, endothelium-dependent vasodilatation is increased in women who have PE to levels over and above those seen in normal pregnancy. 9 After pregnancy, however, both arterial and microvascular endothelial functions are diminished in women who had PE. 10 -12 This suggests that either endothelial dysfunction is present before pregnancy and predisposes women to PE, or that PE induces long-term changes in endothelial function, which could have implications for development of cardiovascular disease in later life.There is no study however, that has examined vascular responses sequentially at different gestations before the clinical syndrome of PE develops and after delivery (to compare maternal from placental influences), and compared these changes to those in women who remain normotensive. The purpose of this study, therefore, was to measure endothelial function at 22, 26, and 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk for PE, based on uterine artery Doppler waveforms at 18 to 20 weeks, and control sub...

Time Course of Maternal Plasma Volume and Hormonal Changes in Women With Preeclampsia or Fetal Growth Restriction

“…20 This similarity suggests a possible causal relationship between reduced plasma volume and abnormal uteroplacental blood flow. In addition, a recent study demonstrated an enhanced microvascular response preceding the clinical onset of PE by several weeks, 21 suggesting that alteration in vascular tone is an early event, at least in PE.…”

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

“…For both the sham and ThS groups, the microvascular tissue blood flow over the small intestine, liver and left kidney was monitored using a laser Doppler probe (Moor instruments Ltd., uK) [6,13]. This technique works by scanning a 2 mW helium-neon laser across the surface of the organs.…”

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

“…Also, it has been suggested that acetylcholine induces vasodilation through stimulation of sensory nerves (Berghoff et al, 2002). Despite conflicting evidence regarding the mechanisms by which the drug causes vasodilatation, ACh is commonly delivered iontophoretically to test endothelial function in a variety of clinical conditions, including diabetes (Arora et al, 1998;Cohen et al, 2008;Hannemann et al, 2002;Morris et al, 1995) , hypertension (Cupisti et al, 2000b;Farkas et al, 2004;Kellogg et al, 1998;Monostori et al, 2010), pre-eclampsia (Blaauw et al, 2005;Eneroth-Grimfors et al, 1993;Khan et al, 2005), Raynauds phenomenon (Anderson et al, 1996;Hettema et al, 2009;Khan and Belch, 1999), renal failure (Cupisti et al, 2000a), HIV (Monsuez et al, 2000) and heart failure (Andersson et al, 2005;Balmain et al, 2007). Also, it has been applied to investigate the effects of smoking (Pellaton et al, 2002), age (Rossi et al, 2002a), gender (Algotsson et al, 1995), hyperoxia (Rousseau et al, 2010;Yamazaki, 2007) and exercise (Lenasi and Strucl, 2004;Rossi et al, 2002b).…”