title: Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat.
abstract: Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension.
authors.affiliation: Institute of Human Nutrition, Southampton General Hospital, Southampton, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Sherman
authors.forename: A A
authors.initials: AA
authors.lastname: Jackson
authors.forename: S C
authors.initials: SC
authors.lastname: Langley-Evans
mesh_terms: D000818:Animals; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D006911:Hydroxyprostaglandin Dehydrogenases; D015232:Dinoprostone