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1 Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, King's College London, UK
2 Centre for the Developmental Origins of Health and Disease (DOHaD), Princess Anne Hospital, Southampton, UK
We recently reported vascular dysfunction in adult offspring of rats fed a fat-rich (animal lard) diet in pregnancy. This study reports further characterization of constrictor and dilator function in mesenteric and caudal femoral arteries from 180-day-old offspring of dams fed the high fat diet (OHF). Endothelium-dependent relaxation in response to acetylcholine (109105M) was impaired in mesenteric small arteries from male and female OHF compared with offspring of dams fed normal chow (males (maximum percentage relaxation): OHF 67.92 ± 2.89, n= 8 versus control 92.08 ± 2.19, n= 8, P < 0.01). Substantial relaxation in response to acetycholine in control mesenteric arteries remained after inhibition of nitric oxide synthase, soluble guanylate cyclase and cyclo-oxygenase but was blocked by 25 mM potassium. This component of relaxation, attributed to EDHF, was significantly reduced in OHF mesenteric arteries compared with controls. However, EDHF played a minor role in acetylcholine-induced relaxation in both control and OHF femoral caudal arteries (male and female). In these arteries, in contrast to mesenteric vessels, acetylcholine-induced relaxation was significantly enhanced in OHF but only in males (ACh (maximum percentage relaxation): OHF 58.40 ± 4.39, n= 8 versus male controls 32.18 ± 6.36, P < 0.05). This was attributable to enhanced nitric oxide-mediated relaxation. In conclusion, reduced endothelium-dependent relaxation in OHF mesenteric arteries is due to impaired EDHF-mediated relaxation. This defect was not apparent in femoral arteries in which EDHF has a less prominent role.
(Received 26 April 2004;
accepted after revision 8 June 2004;
first published online 11 June 2004)
Corresponding author P. D. Taylor: Maternal & Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, 10th Floor North Wing, St Thomas' Hospital, London SE1 7EH, UK. Email: paul.taylor{at}kcl.ac.uk
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