Murine aortic reactivity is programmed equally by maternal low protein diet or late gestation dexamethasone

• Published in: The journal of maternal-fetal & neonatal medicine 2007-01, Vol.20 (11), p.833-841
• Main Authors: Roghair, Robert D., Segar, Jeffrey L., Kilpatrick, Robert A., Segar, Emily M., Scholz, Thomas D., Lamb, Fred S.
• Format: Article
• Language: English
• Subjects: Acetylcholine; Animals; Animals, Newborn; blood pressure; Blood Pressure - drug effects; developmental biology; Dexamethasone - pharmacology; Diet, Protein-Restricted - adverse effects; Disease Models, Animal; Endothelium - drug effects; Endothelium - physiopathology; Female; Fetal Development - drug effects; fetal programming; Glucocorticoids - pharmacology; Glucose Tolerance Test; Male; Mice; Pregnancy; Prenatal Exposure Delayed Effects
• ISSN: 1476-7058; 1476-4954
• DOI: 10.1080/14767050701626540

Objective. In rats, maternal low protein diet induces growth restriction, increases fetal glucocorticoid exposure and programs cardiovascular and endocrine dysfunction in adult offspring. We hypothesized that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop hypertension, vascular dysfunction, and glucose intolerance. Methods. An iso-caloric low protein diet (LP) was provided to dams from E0 to E19. Additional dams received a normal protein diet without (NP) or with either dexamethasone (NP-Dex, 0.1 mg kg d sc) or normal saline (NP-NS) from E10 to E18. Results. Offspring of dams given LP weighed less at 10 days than NP offspring, while Dex administration did not alter pup weight. At 4 months, all four groups had similar systolic blood pressures and no detectable differences were evoked by oral L-NAME. Offspring of LP mice had impaired glucose clearance that was directly correlated with their weight at 10 days. Aortic rings from offspring of both LP and NP-Dex exposed dams had impaired vasodilatation to acetylcholine. Conclusions. These findings demonstrate that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop endothelial dysfunction in the absence of hypertension, while only maternal LP impaired perinatal growth and glucose clearance in adult offspring.