Obesity is associated with increased cardiovascular mortality and morbidity. It causes endothelial dysfunction, which is a marker for coronary-heart disease (Schachinger et al. 2000) and the main cause of death in obese subjects (Suwaidi et al. 2000). Yet surprisingly little work has been done to investigate how it damages the arteries. Here we have studied the role of an energy-rich diet on metabolic changes and arterial contractility.

Male Wistar rats were either fed laboratory chow throughout (control; n = 10); or given a fat-enriched, glucose-enriched diet (Naderali et al. 2001) for 16 weeks (diet-fed; n = 23). After 16 weeks, animals were killed by CO₂ inhalation followed by exsangunation. Trunk blood was collected for later analysis of insulin, glucose, leptin, non-esterified fatty acids (NEFA) and triglycerides. For contractile studies, third-order mesenteric resistance arteries were dissected out and mounted (in duplicate) on a computerised myograph based on Mulvany’s principle.

At the end of the experiment, body weight (647.2 ± 19.0 vs. 574.5 ± 13.0 g), epididymal (19.1 ± 1.1 vs. 12.5 ± 1.2 g) and perirenal (22.3 ± 0.9 vs. 14.3 ± 1.2 g) fat pad masses and heart weights (1.8 ± 0.2 vs. 1.5 ± 0.1 g), but not gastrocnemius muscle (3.2 ± 0.1 vs. 3.1 ± 0.1 g) mass, were significantly (P < 0.001, Student’s paired t test) higher in diet-fed rats than chow-fed controls. Terminal plasma levels of glucose (8.11 ± 0.26 vs. 7.61 ± 0.31 mM) and insulin (8.47 ± 0.91 vs. 8.33 ± 0.63 mU ml^-1) were comparable between the two groups, while diet-fed rats had significantly raised plasma NEFA (0.59±0.06 vs. 0.41±0.05 mM) and triglyceride (0.45 ± 0.07 vs. 0.22 ± 0.2 mM) and leptin (44.9 ± 2.7 vs. 22.4 ± 3.9 ng ml^-1) levels (by >100% P < 0.0001 paired t test). Myograph studies of mesenteric arteries showed that vasoconstrictor responses to noradrenaline (0.5-6 µM) and KCl (10-125 mM) were comparable between two groups indicating that diet and dietary-induced obesity had no effects on arterial contractility. However, both endothelium-dependent and -independent vasorelaxation responses were markedly attenuated in diet-fed rats. Vasorelaxation responses to carbamylcholine (10 mM to 100 µM) were significantly (> 16% P < 0.01 ANOVA) attenuated in the diet-fed group suggesting endothelial dysfunction. Sodium nitroprusside-induced vasorelaxation (10 nM to 100 µM) was also significantly (> 10% P < 0.05 ANOVA) decreased in the diet-fed group indicating abnormalities in vascular smooth muscle cells.

In conclusion, feeding rats with an energy-rich diet causes obesity and marked arterial dysfunction associated with it, an effect that may be mediated by raised leptin, NEFA and/or triglyceride levels.