Cholesterol-independent endothelial dysfunction in virgin and pregnant rats fed a diet high in saturated fat.
1. Western diets high in saturated fat are associated with an increased incidence of cardiovascular diseases. In this study we have evaluated vascular endothelial function and oxidative stress in virgin rats fed a normal (VC) or high in saturated fat diet (VHF) (20 % lard and corn oil w/w) from weaning until adulthood, and throughout subsequent pregnancy (PC and PHF, respectively). 2. The saturated fat diet was associated with enhanced noradrenaline sensitivity in small mesenteric arteries from VHF rats (VHF vs. VC, P < 0.05) and blunted endothelium-dependent relaxation in VHF and PHF rats (VHF vs. VC, P < 0.001; PHF vs. PC, P < 0.05). Endothelial dysfunction was attributable to a reduced nitric oxide component of relaxation in VHF rats, and blunted prostacyclin and endothelium-derived hyperpolarizing factor components in PHF rats. 3. Other than plasma cholesterol, which was reduced in VHF and PHF rats, plasma lipids were normal. Fasting plasma insulin and glucose concentrations were raised in VHF rats (P < 0.05) and the plasma marker of oxidative stress, 8-iso PGF2alpha, was increased in PHF animals (P < 0.01). 4. These findings suggest that endothelial dysfunction induced by a saturated fat diet is cholesterol independent and likely to be of different mechanistic origin in virgin and pregnant rats.
Gerber
R T
RT
Department of Obstetrics and Gynaecology, Guy's, King's and St Thomas' School of Medicine (GKT), St Thomas' Hospital, London, UK.
Holemans
K
K
O'Brien-Coker
I
I
Mallet
A I
AI
van Bree
R
R
Van Assche
F A
FA
Poston
L
L
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D028441:F2-Isoprostanes; D005227:Fatty Acids / Q000008:administration & dosage* / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007328:Insulin / Q000097:blood; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D028441:F2-Isoprostanes; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; C075750:8-epi-prostaglandin F2alpha; D002784:Cholesterol; D015237:Dinoprost