title: Impaired EDHF-mediated vasodilatation in adult offspring of rats exposed to a fat-rich diet in pregnancy.
abstract: 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 (10(-9)-10(-5)m) 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.
authors.affiliation: Maternal & Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, 10th Floor North Wing, St Thomas' Hospital, London SE1 7EH, UK. paul.taylor@kcl.ac.uk
authors.forename: P D
authors.initials: PD
authors.lastname: Taylor
authors.forename: I Y
authors.initials: IY
authors.lastname: Khan
authors.forename: M A
authors.initials: MA
authors.lastname: Hanson
authors.forename: L
authors.initials: L
authors.lastname: Poston
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D004041:Dietary Fats / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001685:Biological Factors; D004041:Dietary Fats; C067410:endothelium-dependent hyperpolarization factor; D000109:Acetylcholine