Endothelium-Dependent Relaxation and Angiotensin II Sensitivity in Experimental Preeclampsia

Anne Marijn Van Der Graaf,Azuwerus Van Buiten,Torsten Plösch,Marijke M Faas,Hendrik Buikema,Marjon J Wiegman,Robert H Henning,Gerda G Zeeman,Ana Claudia Zenclussen

doi:10.1371/journal.pone.0079884

Anne Marijn Van Der Graaf, Azuwerus Van Buiten + Show 7 more

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https://doi.org/10.1371/journal.pone.0079884

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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.

Highlights

Preeclampsia is a pregnancy specific syndrome, clinically characterized by the presence of hypertension, associated with proteinuria in the second half of pregnancy [1]
The model used for experimental preeclampsia, i.e. the low dose LPSinfused pregnant rat is an established model for preeclampsia, which has been used for many years [25,26]
We found that during pregnancy, there appeared to be a decreased role for contractile PG and a decreased role for endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced relaxation of the aorta as compared to the non-pregnant state

Summary

Introduction

Preeclampsia is a pregnancy specific syndrome, clinically characterized by the presence of hypertension, associated with proteinuria in the second half of pregnancy [1]. Vascular function changes dramatically; increased endothelium dependent vascular relaxation as well as increased flow mediated dilation can be observed [7]. Together this may result in a decrease in blood pressure (mainly in the second trimester) and a decrease in peripheral vascular resistance [8]. There is increasing evidence that the AT2-R may exert an inhibitory influence on AT1-R mediated stimulation [20] It is largely unknown if and how these receptors are involved in the changes in Ang-II sensitivity during normal pregnancy and preeclampsia. This model is characterized by hypertension and proteinuria and has been used as a model for preeclampsia for many years and was used in many studies [21,25,26,27], including a recent study by Wang et al.[28]

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