Excessive maternal fat intake is common in Western populations. Fatty streaks have been reported in fetal aortas from hypercholesterolaemic mothers, suggesting that high-fat intake during pregnancy may predispose offspring to cardiovascular disease (Napoli et al. 1997). We have previously demonstrated abnormalities in plasma lipids, vascular fatty acids (Ghosh et al. 2001), and vascular dysfunction (Koukkou et al. 1998) in the offspring of rats fed a high-fat diet during pregnancy. We aimed to investigate whether the vascular dysfunction was indeed due to the raised maternal dietary fat per se or due to the effective dilution (w/w) of vitamins and nutrients.

Female Sprague-Dawley rats were fed either a control breeding diet (BD, 5 % fat), a high-fat diet (25 % fat), or a high-fat diet supplemented with all vitamins and nutrients to similar levels as the BD. Experimental diets were fed for 10 days prior to and throughout pregnancy and weaning. Thereafter, offspring were fed standard BD (5 % fat) until 80 days of age when animals were humanely killed and isolated mesenteric arteries mounted on a small vessel myograph (approximately 200 µm). Contractile function was assessed by investigating concentration-responses to potassium (K), noradrenaline (NA) and U46619. Endothelium-dependent and -independent relaxation was assessed following preconstriction to NA, by the responses to acetylcholine (ACh) and to native nitric oxide (NO), respectively. Values are given as means ± S.E.M. Statistical comparisons were by ANOVA with Bonferroni correction for multiple comparison.

Contractile function in these arteries was not different between the groups. Maximal relaxation to ACh was blunted in the male offspring of dams fed the high-fat diet compared with controls (% relaxation: con, 84.58 ± 3.21 (n = 11) vs. high-fat, 60.31 ± 4.56 (n = 12), P < 0.01, but was not improved by supplementation, 67.60 ± 3.70 (n = 12), P < 0.05). There was a significant but less marked trend in the female offspring (% relaxation: con, 80.74 ± 5.23 (n = 11) vs. high-fat, 59.49 ± 7.48 (n = 12) vs. supplemented, 63.10 ± 5.00 (n = 12); ANOVA, P = 0.04).

In conclusion, a high-fat diet fed throughout pregnancy and weaning results in resistance artery endothelial dysfunction in the normally fed offspring and was not reversed by fortification of the maternal diet with vitamins and nutrients.This work was funded by the British Heart Foundation.

Ghosh, P., Bitsanis, D., Ghebremeskel, K., Crawford, M.A. & Poston, L. (2001). J Physiol. 533, 815-822.

Koukkou, E., Ghosh, P., Lowy, C. & Poston, L. (1998). Circulation 98, 2899-2904.

Napoli, C., D’Armiento, F.P., Mancini, F.P., Postiglione, A. & Witzum, J.L. (1997). J. Clin. Invest. 100, 2680-2690.