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Fetal Physiological Programming
1Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH; 4School of Biosciences, University of Nottingham, Sutton Bonington Campus, Nottingham LE12 5RD; 2Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH; 3AstraZeneca, Alderly Park, Cheshire SK10 4TF, United Kingdom; and 5Department of Animal Sciences, University of Missouri, Columbia, Missouri 65211
Submitted 1 December 2003 ; accepted in final form 10 February 2004
The prenatal nutritional environment influences the subsequent risk of hypertension in adulthood. Animal studies have used, generally, the rat as a model species to illustrate the association between maternal nutrient intake and blood pressure in the resulting adult offspring. No study to date has shown programming of adult cardiovascular function in the sheep through maternal dietary intervention. We therefore fed pregnant sheep to either 100% recommended intake from day 0 of gestation to term [
147 days gestational age (dGA); controls n = 8] or to 50% recommended intake from day 0 to 95 dGA and thereafter to 100% intake (NR; n = 9). Sheep lambed naturally, offspring were weaned at 16 wk, and the male offspring were reared on pasture until 3 yr of age. At this time, cardiovascular catheters were inserted under halothane anesthesia and sheep were allowed 2–4 days recovery. Basal cardiovascular status and pressor responses to infusion of norepinephrine, angiotensin II, and captopril were then assessed alongside basal plasma concentrations of glucose, cortisol, and leptin. NR sheep were of similar birth weight to controls but at 3 yr of age had higher blood pressure before, but not after, feeding. Peripheral sensitivity to vasoconstrictor infusion was similar between dietary groups, although a reflex bradycardia was not apparent in NR sheep during norepinephrine infusion. Circulating leptin correlated well with fat mass and increased more after vasoconstrictor infusion in NR sheep. In conclusion, early NR has been shown to program aspects of cardiovascular control and adipocyte function in adult sheep.
nutrition; norepinephrine; sympathetic nervous system; blood pressure; leptin
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