Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study

BACKGROUND: Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats. METHODS: Male Wistar rats (n = 6/group) were fed diets providing varying percentages of energy from fat and carbohydrate (CHO). For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO), chow supplemented with chocolate biscuit (30% fat; 56% CHO) or a high-fat diet (45% fat; 35% CHO). Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA). RESULTS: Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p < 0.01) and elevated concentrations of TGs and NEFAs (+41% and +17%; both p < 0.05). High-fat-fed animals showed an increase only in NEFAs (+38%; p < 0.01). Arterial vasoconstriction in response to NA and KCl increased only in biscuit-fed rats (both p < 0.01), while vasorelaxation in response to CCh and SNP, but not histamine, was attenuated in both groups (both p < 0.01). Furthermore, whereas the effect of the high-fat diet was most pronounced in endothelium-dependent vasorelaxation, the biscuit diet had the greater effect on endothelium-independent vasorelaxation. CONCLUSION: Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.