Fetal programming effects of pentaerythritol tetranitrate in a rat model of superimposed preeclampsia
- PDF / 1,789,927 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 34 Downloads / 162 Views
ORIGINAL ARTICLE
Fetal programming effects of pentaerythritol tetranitrate in a rat model of superimposed preeclampsia Andy W. C. Man 1 & Min Chen 1,2 & Yawen Zhou 1 & Zhixiong Wu 1 & Gisela Reifenberg 1 & Andreas Daiber 3,4 & Thomas Münzel 3,4 & Ning Xia 1 & Huige Li 1 Received: 6 February 2020 / Revised: 29 June 2020 / Accepted: 9 July 2020 # The Author(s) 2020
Abstract Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFDinduced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes. Key messages The core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to • Improvement of fetal growth; • No changes of maternal blood pressure or markers of preeclampsia; • Amelioration of HFD-induced glucose intolerance in adult offspring; • No changes in blood pressure development of the offspring on normal chow or high salt-diet; • Potentiation of blood pressure elevation of the offspring on HFD. Keywords Fetal programming . Epigenetics . Dahl salt-sensitive rats . Pentaerythritol tetranitrate . Vascular function Andy W. C. Man and Min Chen contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00109-020-01949-0) contains supplementary material, which is available to authorized users. * Ning Xia [email protected] * Huige Li [email protected] 1
Department of Pharmacology, Johannes Gutenberg University Medical Center, Langenbeck Str. 1, 55131 Mainz, Germany
2
Department of Anaesthesiology, Institute of Anae
Data Loading...
