title: Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.
abstract: Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Jiunn-Ming
authors.initials: JM
authors.lastname: Sheen
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hong-Ren
authors.initials: HR
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ching-Chou
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Department of Traditional Chinese Medicine, Chang Gung University, Linkow, Taiwan.
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003907:Dexamethasone / Q000009:adverse effects / Q000819:agonists*; D059305:Diet, High-Fat / Q000009:adverse effects; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007850:Lauric Acids / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C504897:12-(3-adamantan-1-ylureido)dodecanoic acid; C477819:15-deoxyprostaglandin J2; D007850:Lauric Acids; D044139:Receptor, Angiotensin, Type 2; D016718:Arachidonic Acid; D009569:Nitric Oxide; D003907:Dexamethasone; D004851:Epoxide Hydrolases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000218:Adamantane; D015230:Prostaglandin D2
keywords: Arachidonic acid; Developmental programming; Fat; Glucocorticoid; Hypertension; Nitric oxide; Renin–angiotensin system