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


BACKGROUND
Acetylcholine; blood pressure; developmental biology; fetal programming
Roghair
Robert D
RD
Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
Segar
Jeffrey L
JL
Kilpatrick
Robert A
RA
Segar
Emily M
EM
Scholz
Thomas D
TD
Lamb
Fred S
FS
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D005938:Glucocorticoids; D003907:Dexamethasone