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 inc idence 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 weani ng until adulthood, and throughout subsequent pregnancy (PC and PHF, respec tively). 2. The saturated fat diet was associated with enhanced noradrenaline sensit ivity 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 P HF rats. 3. Other than plasma cholesterol, which was reduced in VHF and PHF rats, pl asma lipids were normal. Fasting plasma insulin and glucose concentrations were raised in VHF rats (P < 0.05) and the plasma marker of oxidative stres s, 8-iso PGF(2 alpha), was increased in PHF animals (P < 0.01). 4. These findings suggest that endothelial dysfunction induced by a saturat ed fat diet is cholesterol independent and likely to be of different mechan istic origin in virgin and pregnant rats.