Prenatal dexamethasone-induced programmed hypertension and renal programming

Jiunn-Ming Sheen; Hong-Ren Yu; Mao-Meng Tiao; Chih-Cheng Chen; Li-Tung Huang; Hsin-Yu Chang; You-Lin Tain

doi:10.1016/j.lfs.2015.04.005

Prenatal dexamethasone-induced programmed hypertension and renal programming

Life Sci. 2015 Jul 1:132:41-8. doi: 10.1016/j.lfs.2015.04.005. Epub 2015 Apr 25.

Authors

Jiunn-Ming Sheen¹, Hong-Ren Yu¹, Mao-Meng Tiao¹, Chih-Cheng Chen¹, Li-Tung Huang², Hsin-Yu Chang¹, You-Lin Tain³

Affiliations

¹ Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
² Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Traditional Chinese Medicine, Chang Gung University, Linkow, Taiwan.
³ Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.

PMID: 25921765
DOI: 10.1016/j.lfs.2015.04.005

Abstract

Aims: Antenatal glucocorticoids can induce long-term effects on offspring health, including hypertension. Programmed hypertension has been observed in a prenatal dexamethasone (DEX) exposure model. However, how renal programming responds to prenatal DEX at different stages of development and the impact of DEX on programmed hypertension remain unclear. Therefore, we utilized RNA next-generation sequencing (NGS) to analyze the renal transcriptome in the offspring to examine whether key genes and pathways are responsible for DEX-induced renal programming and hypertension.

Main methods: Pregnant rats received intraperitoneal dexamethasone from gestational day 16 to 22. Prenatal DEX-induced programmed hypertension was examined in male offspring at 16 weeks of age.

Key findings: Prenatal DEX modified 431 renal transcripts from the nephrogenesis stage to adulthood in a constant manner. At the pre-hypertensive and established hypertension stages, we identified 11 and 13 differentially expressed genes related to blood pressure regulation, respectively. Among these genes, Npr3, Ptgs2, Agt, Edn3, Ephx2, Agtr1b, and Gucy1a3 are associated with endothelium-derived hyperpolarizing and contractile factors (EDHF and EDCF). Genes in the arachidonic acid metabolism pathway may potentially be key genes contributing to programmed hypertension. In addition, DEX induced soluble epoxide hydrolase expression (Ephx2 gene encoding protein).

Significance: Prenatal DEX elicits an imbalance between EDHFs and EDCFs that might lead to renal programming and hypertension. The arachidonic acid metabolism pathway is a common pathway contributing to programmed hypertension. Our results highlight candidate genes and pathways involved in renal programming as targets for therapeutic approaches to prevent programmed hypertension in children exposed to antenatal corticosteroids.

Keywords: Arachidonic acid; Endothelium-derived contractile factor; Endothelium-derived hyperpolarizing factor; Glucocorticoid; Hypertension; Next-generation sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arachidonic Acid / metabolism
Blood Pressure / genetics
Blotting, Western
Dexamethasone / administration & dosage
Dexamethasone / adverse effects*
Female
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Hypertension / chemically induced*
Injections, Intraperitoneal
Kidney / drug effects*
Kidney / metabolism
Male
Pregnancy
Prenatal Exposure Delayed Effects / pathology*
Rats
Real-Time Polymerase Chain Reaction
Transcriptome / drug effects*

Substances

Arachidonic Acid
Dexamethasone