Abstract 1137: Switch From Nitric Oxide To Hydrogen Peroxide Mediated Dilation In Coronary Arterioles Of Obese Rats

Abstract

Background. Obesity is associated with coronary endothelial dysfunction, an early marker of atherosclerosis; but impaired endothelial function in obese Zucker rats appears not to be mediated by NO production. Hypothesis: We tested the hypothesis that endothelial derived hyperpolarizing factor (EDHF) is responsible for endothelial dilation in obese rats. Methods: We used 4 groups of male Zucker rats: lean and obese on normal and low carb diets. Rats were fed ad libitum for 3 weeks; caloric intake and weight gain were similar. Coronary arterioles were cannulated and pressurized for diameter measurements. Vasodilation to acetylcholine (Ach) and flow was determined before and after incubation with L-NAME (10 μm), an inhibitor of NO synthase, plus the cyclooxygenase inhibitor indomethacin (Indo; 10 μm), after tetraethylammonium (TEA 1 mM), a non-selective K + channel antagonist, and after catalase, a H 2 O 2 scavenger (CAT; 500 U/ml). Results Acetylcholine-induced vasodilation was impaired in obese rats compared to lean (41%; n=5 vs 87%; n=3; p<0.05) and did not change after L-NAME+Indo incubation in obese both on normal (47 ± 19%; n = 4 vs . 40 ± 13%; n = 4; p =ns) and low carb diet (51 ± 1%; n = 3 vs . 59 ± 6%; n = 3; p =ns). Flow-induced dilation was impaired in obese rats compared to lean (38%;n=5 vs 78%; n=2;p<0.05) and this dilation was not affected by L-NAME+Indo incubation in obese both on normal (45±12%; n=4 vs 48±10% n=4; p =ns) and low carb diet (53±14%; n=3 vs 61±12% n=3; p =ns). Importantly, TEA incubation decreased Ach dilation both in obese on normal (41±11%; n=5 vs 13±7% n=5; p< 0.05) and low carb diet (76±25%; n=3 vs 22±18% n=3; p< 0.05). Similar results were obtained during flow-induced dilation in obese both on normal (37±17%; n=5 vs 14±7% n=5; p< 0.05) and low carb diet (54±14%; n=3 vs 15±3% n=3; p< 0.05). Catalase administration blocked both FID and Ach dilation in obese both on normal (FID 45±15% vs 5±3% n=3; p< 0.05; Ach 39±14% vs 12±5% n=3; p<0.05) and low carb diet (FID 52±19% vs 18±7% n=2; p< 0.05; Ach 75±35% vs 15±2% n=2; p< 0.05). Conclusions: Endothelial dependent vasodilation of coronary arterioles in obese Zucker rats is mediated by H 2 O 2 and increases in endothelial function in obese rats on a low carb diet is mediated by increased H 2 O 2 -induced dilation.