Abstract 18339: Weight Loss with Low Carbohydrate Diets Improves Flow Induced Vasodilation in Resistance Arteries

Abstract

Introduction: Obesity is associated with microvascular dysfunction and reduced nitric oxide (NO). We tested the hypothesis that NO-dependent, flow induced vasodilation in microvessels is improved by low carbohydrate diets designed for weight loss. Methods: Obese female adults (BMI = 32.0 ± 0.6 kg/m 2 , pre & post, n=22) were randomly assigned to a low carbohydrate (LC) diet for weight loss (LCWL, n=11, 500 calorie/day deficit). All meals were prepared for 6 weeks (10% carbohydrate, 30% protein, 60% fat). Resistance arteries (RAs, internal diameter of 16021 μm, n=22) were dissected from gluteal subcutaneous fat biopsies at weeks 0 (pre) and 6 (post). Vessels were cannulated and exposed to pressure gradients (Δ10-Δ100 cmH 2 O), with or without L-NAME (10 -4 M, inhibitor of eNOS), PEG-catalase (PEG-CAT, 500 Units/ml, scavenger of H 2 O 2 ), indomethacin (INDO, 10 -5 M, inhibitor of cyclooxygenase), or pioglitazone (PIOG, 10 -5 M, PPARγ agonist) and to papaverine (10 -4 M), pre and post LC. NO or H 2 O 2 in RAs was measured by fluorescence microscopy. Results: LC diets reduced BMI (post 32.7±0.8% vs. pre 31.4±1.0%, p<0.01), and increased flow-induced vasodilation (FID, post 81 ± 3% vs. pre 63 ± 4%, at Δ100 cmH 2 O (p<0.01) that was reduced by L-NAME and PEG-CAT (p<0.05). Consistently, vascular NO (fluorescence ratio: 1.5 ± 0.3, post vs. pre, p<0.05) and H 2 O 2 (2.6 ± 1.2, p<0.05) were increased with flow, and inhibited by L-NAME and PEG-CAT, respectively. INDO reduced FID in post, less (p<0.05) than in pre LC. There was no effect of pioglitazone on FID both in pre and in post (p>0.05). Endothelium independent responses to papaverine were similar in pre and post LC. Conclusion: We found that after 6 weeks of WL on low carbohydrate diet, 1) BMI was reduced, and microvascular vasodilator reactivity was improved; 2) microvascular NO and H 2 O 2 generation were increased; and 3) there was no effect of pioglitazone on FID in resistance arteries. These data indicate that weight reduction on low carbohydrate diet is critical for improved and endothelium-dependent microvascular function. NIH ( R01HL095701 ).