Coronary and Mesenteric Vascular Dysfunction in High Fat Fed Rats

Abstract

The purpose of this study was to examine microvascular complication in rats fed a high fat (HF) diet. Sprague‐Dawley rats 12 weeks of age were fed a diet containing 45% kcal as fat. Reactivity of small (75 – 150 μm intraluminal diameter) coronary and mesenteric vessels was evaluated. After 8 weeks, vascular relaxations were not altered. After 16 weeks, acetylcholine (ACh)‐mediated relaxation of coronary arteries from HF fed rats was impaired (relaxation to 10 μM Ach: control=47 ± 5, high fat fed=27 ± 8%, p≤0.05). After 24 weeks, reactivity of coronary arteries to ACh was further impaired in rats fed the HF diet (relaxation to 10 μM Ach: control=47 ± 9, HF fed=14 ± 13%, p≤0.05). After 32 weeks on the diet, 10 μM ACh induced 42 ± 28 and 23 ± 8% relaxation in coronary arteries from control and HF fed rats, respectively. Hydroethidine staining suggests increased superoxide formation in coronary arteries from HF fed rats. ACh‐mediated responses were not altered in mesenteric arteries from HF fed rats for the first 24 weeks. After 32 weeks on the diets, 10 μM Ach induced 89 ± 4 and 54 ± 13% relaxation in mesenteric arteries from control and HF fed rats, respectively, p≤0.05. Reversal of diet for 8 weeks, after 24 weeks on HF diet, did not improve vascular function. These studies suggest that a HF diet causes a progressive impairment of endothelium‐dependent vascular function in small arteries. Supported by VA Merits to Drs. Oltman and Yorek.