New conception for the development of hypertension in preeclampsia

Abstract

Placental vascular dysfunction was suggested to be critical for placental ischemia-initiated hypertension in preeclampsia, although the contributions of endothelium involved are unclear. The present study found, unlike non-placental vessels, acetylcholine showed no vasodilatation effect on placental vessels, indicating that endothelial-derived nitric oxide (NO) was extremely weak in placental vessels. Placental vascular responses to exogenous NO from sodium nitroprusside (SNP) were significantly different from non-placental vessels. These results were further confirmed in sheep, and rat vessels. In preeclamptic placental vessels, acetylcholine also showed no vasodilatation effects, while vascular responses to SNP were suppressed, associated with impaired cGMP/sGC pathway in vascular smooth muscle cells (VSMCs). The current theory on placental ischemia-initiated hypertension in preeclampsia focused on changes in placental vascular functions, including endothelial dysfunction. This study found the placental endothelium contributed very poorly to vasodilatation, and altered vascular functions in preeclampsia mainly occurred in VSMCs instead of endothelial cells. The findings contribute importantly to understanding the special feature of placental vascular functions and its pathophysiological changes in the development of hypertension in preeclampsia.

The role of α2‐adrenergic receptors in hypertensive preeclampsia: A hypothesis

“…It is important to note, however, that NO still plays a role in the vasodilation of the placental vasculature. Indeed, endothelium‐independent vasodilation, expressed as the vasodilatory response to the NO donor SNP, although reduced, was still present in preeclamptic placental vessels . This indicated that it might be the smooth muscle portion of the NO‐dependent vasodilatory pathway that is altered in preeclamptic vessels.…”

“…NO is a principal vasodilator released by ECs and diffuses to the underlying VSMC layer triggering vasorelaxation . Because of its potency in mediating vasorelaxation, several studies aimed at understanding the role of NO in the isolated UA of PE animal models and in human placental vessels . However, these studies have revealed inconsistent results with controversy regarding the presence or absence of NO‐induced vasodilation in PE.…”

“…Yet, other studies deduced that reduced NO production cannot account for increased vasoconstriction of preeclamptic uterine vessels, due to the notion that decidual ECs from preeclamptic pregnancies did not produce less NO than cells from normal pregnancies . Interestingly, a recent study showed that the placental vasculature lacks its own endogenous endothelium‐derived NO . In contrast to human nonplacental vessels, ACh showed no vasodilatory effect on human placental vessels.…”

“…Activation of α 2 ‐ARs has been linked to activation of Ca 2+ ‐activated (K Ca ) and GIRK K + channels . Indeed, in VSMCs from placental vessels, SNP evoked an increase in whole‐cell K + currents that was comparable to nonplacental VSMCs, and that effect was weaker in placental VSMCs from preeclamptic pregnancies . Moreover, endothelial K Ca channels are downregulated by serum factors as a result of ROS generation in PE, which may contribute to the pathogenesis .…”

“…84 Interestingly, a recent study showed that the placental vasculature lacks its own endogenous endothelium-derived NO. 82 In contrast to human nonplacental vessels, [85][86][87] ACh showed no vasodilatory effect on human placental vessels. This was also consistent with results from sheep and rat vessels examined in the very study.…”