BH4 Restores NO Generation in Resistance Arteries in Obese Individuals

Background and Aims: (6R)-5, 6, 7, 8-tetrahydrobiopterin (BH 4 ), co-factor of endothelial nitric oxide synthase (eNOS) plays a crucial role in the generation of NO. Previous studies indicate that obesity contributes to endothelial dysfunction and impairs the production of NO. The aim of this study was to determine if BH 4 supplementation to isolated resistance arteries from visceral fat of obese patients restores NO generation. Methods : Abdominal visceral fat were obtained during bariatric weight loss surgery from women (BMI > 35 kg/m 2 visceral arterioles were isolated from visceral fats, cannulated in an organ chamber. Arteriole diameter measurements ( m m) were assessed in response to flow (pressure gradients of 10-100 cmH 2 O) with and without L-NAME, PEG-CAT, and BH 4 . Arterioles were maintained at a pressure of 60 cm H 2 O for 30 minutes for myogenic stability with or without BH 4 (10μM), L-Name (500 m M), and PEG-CAT (500 m M) incubation. NO generation were detected in visceral arterioles using a NO detection dye (2μL diluted in 2ml of HEPES, as final 5μM) and examined under fluorescence microscopy. ImageJ program was used for measurement of NO intensity. Student T-Test was used and P value was less than 0.01 as significant. Result: FID arterioles induced with BH 4 had a significant increase in vasodilation % compare to baseline. Vasodilation % in BH 4 + L-NAME compare to baseline was not significantly different, indicating NO production was blocked by L-NAME in the presence of BH 4 . BH 4 + PEG-catalyse compare shows a significant increase in vasodilation, suggesting that NO was produced and not H 2 O 2. NO intensity in BH 4 was significantly increased (46±5 Arbitrary Units (AU), p<0.01) in comparison to baseline (12±4 AU). Conclusion: These data suggest that exogenous BH 4 increases NO generation in resistance arteries from visceral adipose tissue, indicating endogenous BH 4 is deficient in human obesity. Keywords: BH 4 , obesity, adipose, blood flow, nitric oxide, biochemistry, endothelium, visceral arteriole