Endothelium-Dependent Relaxation and Angiotensin II Sensitivity in Experimental Preeclampsia

Abstract

ObjectiveWe investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat.MethodsAortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine--mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, NG-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR.ResultsThe role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia.ConclusionPregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.

Upregulation of P53 promoted G1 arrest and apoptosis in human umbilical cord vein endothelial cells from preeclampsia

“…To date, although the potential mechanisms underlying the pathogenesis of preeclampsia remain unclear, endothelial cellular injury has become a major research focus of the pathogenetic processing implicated in preeclampsia [6,7]. About the pathogenesis of preeclampsia, current research has aimed at the imbalance between vasodilator and vasoconstrictor substances produced by the endothelium [8,9]. However, information is limited regarding the vascular endothelial cells in placental–umbilical cord circulation in preeclampsia, including cellular proliferation, migration, and formation of capillary-like tube structures.…”

Experimental preeclampsia in rats affects vascular gene expression patterns

“…Experimental preeclampsia in rats induced with low-dose LPS during pregnancy is one of the main models to study the effects of preeclampsia on both the mother and the offspring 15 , 18 , 29 – 33 . We choose to use the aorta, since the aorta is easily accessible and often used for studies of vascular function in pregnancy, including our own studies 15 , 34 – 36 . The aorta, however, is a typical conductance vessel, rather than a resistance vessel associated with blood pressure regulation.…”

“…We recently studied endothelial function in the low dose LPS infused rat model for preeclampsia 15 . We have shown that the pregnancy-induced changes in endothelial function, such as an increased role of contractile prostaglandins and a decreased role of EDHF in acetylcholine-induced endothelial vasodilation as well as a decreased sensitivity to angiotensin II (angII), were not observed in the preeclamptic rat model 15 . Also in humans, similar changes occur in healthy pregnancy, while a lack of these changes are found in preeclamptic patients.…”

The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

“…Moreover, the response in Wistar rats appears to model the response seen during normal pregnancy in healthy women, whereas the response in Sprague-Dawley rats appears to model the response of women showing vascular maladaptation, such as preeclampsia. This finding underlines that researchers designing new animal experiments must be clear about which aspects of a condition they want to study and must be careful in selecting a species or strain of laboratory animal ( van der Graaf et al 2013 ).…”