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. KEYWORDS: Acetylcholine; blood pressure; developmental biology; fetal programming
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. KEYWORDS: Acetylcholine; blood pressure; developmental biology; fetal programming
Authors: Andrew W Norris; Chunlin Wang; Jianrong Yao; Susan A Walsh; Alexander B Sawatzke; Shanming Hu; John J Sunderland; Jeffrey L Segar; Laura L B Ponto Journal: Endocrinology Date: 2010-11-17 Impact factor: 4.736
Authors: Robert D Roghair; Jeffrey L Segar; Kenneth A Volk; Mark W Chapleau; Lindsay M Dallas; Anna R Sorenson; Thomas D Scholz; Fred S Lamb Journal: Am J Physiol Regul Integr Comp Physiol Date: 2009-01-14 Impact factor: 3.619