Developmental regulation of cardiovascular function is dependent on both genotype and environment.
Adverse developmental environments can increase the risk of adult cardiovascular disease, but not all individuals are affected, suggesting the importance of genotype. Genetically distinct mouse strains allow the genetic dissection of complex traits; however, they have not been used to evaluate the developmental origins of adult cardiovascular disease. Our objective was to determine the effect of prenatal nutrient restriction (R) on adult cardiovascular function in A/J (AJ) and C57BL/6J (B6) mice and whether a postnatal high-fat (HF) diet exacerbates these effects. Pregnant AJ and B6 mice underwent a 30% R or ad libitum diet, and their offspring underwent a HF or control diet. Hypertension (+17 mmHg; P<0.001) was observed in B6R mice at 9 wk, and their arterial pressure tended to remain high at 25 wk (+13 mmHg; not significant). In AJR mice, the normal decrement in arterial pressure over this age range in this strain was abolished. Heart rate prematurely increased in B6R and decreased in AJR (all; P<0.05) mice from 9 to 25 wk. There was no effect of postnatal HF diet on these relationships. The Tei index (from a 26-wk microultrasound) was increased in both AJR and B6R mice (all; P<0.05), suggesting an improved global myocardial performance. Neither R nor HF alone changed diastolic (ratio of E wave to A wave) or systolic (%fractional shortening) function in either strain; however, R and HE combined improved diastolic function in B6 (P<0.05) but not in AJ mice. Therefore, there are strain-dependent alterations in adult cardiovascular function in response to prenatal nutrient restriction. Unexpectedly, a postnatal HF diet did not exacerbate the effects of prenatal nutrient restriction on postnatal cardiovascular outcomes.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Physiology, University of Toronto, 25 Orde St. Ste. 6-1004, Toronto, ON, M5T 3H7, Canada.
Brian S
BS
Knight
Nana
N
Sunn
Craig E
CE
Pennell
S Lee
SL
Adamson
Stephen J
SJ
Lye
D000367:Age Factors; D000375:Aging; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000196:embryology / Q000235:genetics* / Q000503:physiopathology; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000196:embryology / Q000254:growth & development / Q000503:physiopathology*; D004041:Dietary Fats / Q000009:adverse effects*; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006339:Heart Rate / Q000235:genetics; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000235:genetics; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D013045:Species Specificity; D014463:Ultrasonography
D004041:Dietary Fats