Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 38, Issue -, Pages 86-92Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2016.08.006
Keywords
Arachidonic acid; Developmental programming; Fructose; Hypertension; Nitric oxide; Renin-Angiotensin system; Soluble epoxide hydrolase
Funding
- Chang Gung Memorial Hospital, Kaohsiung, Taiwan [CMRPG8F0021, CMRPG8C0043]
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Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-l-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Delta(12.14)-prostagandin J(2) (15dPGJ(2)) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ(2). In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ(2) group, male offspring received 15dPGJ(2) 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ(2) treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE(2) levels in adult offspring kidney exposed to maternal HF. 15dPGJ(2) therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake. (C) 2016 Elsevier Inc. All rights reserved.
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