Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet.
1. In the rat low birthweight and raised systolic blood pressure are the consequence of fetal exposure to maternal low protein diets. Nutritional down-regulation of the placental isoform of 11 beta-hydroxysteroid dehydrogenase, which may increase exposure of the fetus to maternal glucocorticoids, has been suggested to underlie effects of low protein diets on fetal growth and blood pressure. 2. Pregnant rats were fed control (18% casein) or low protein (9% casein) diets throughout gestation. Animals fed the control diet were injected with carbenoxolone, an inhibitor of 11 beta-hydroxysteroid dehydrogenase. Injections were administered either throughout pregnancy (day 0-22), or targeted to specific periods in early (days 0-7), mid- (days 8-14) or late (days 15-22) gestation. 3. Exposure to a low protein diet reduced birthweight and at 4 weeks of age systolic blood pressure was significantly elevated in the rats exposed to low protein. These hypertensive animals had small kidneys in proportion to body weight. 4. Fetal exposure to carbenoxolone at any period in gestation resulted in lower weight at birth. In rats exposed to the inhibitor over days 8-14, 15-22 or 0-22 systolic blood pressure at 4 weeks was significantly higher than in control animals. The greatest elevation of pressure was associated with carbenoxolone treatment in late (days 15-22) gestation. Animals with carbenoxolone-induced hypertension did not exhibit evidence of retarded renal growth. 5. Increased fetal exposure to maternal glucocorticoids impairs fetal growth and programmes elevated blood pressure in later life.
Langley-Evans
S C
SC
Department of University Medicine, Southampton General Hospital, UK.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D000831:Animals, Newborn; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D001724:Birth Weight / Q000187:drug effects*; D002229:Carbenoxolone / Q000009:adverse effects*; D018753:Diet, Protein-Restricted; D004198:Disease Susceptibility; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D006973:Hypertension / Q000139:chemically induced* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000897:Anti-Ulcer Agents; D005938:Glucocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone