摘要
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-Δ12,14-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 (0.1 mg/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 25 mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/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.
原文 | 英語 |
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頁(從 - 到) | 1-8 |
頁數 | 8 |
期刊 | Prostaglandins and Other Lipid Mediators |
卷 | 124 |
DOIs | |
出版狀態 | 已出版 - 01 07 2016 |
文獻附註
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