Impaired vasodilation of human obese visceral resistance arteries is improved by apocynin through hydrogen peroxide and activation of SK and IK channels

Abstract

Previous studies indicate that in human obesity, visceral adipose tissue (VAT) is associated with endothelial dysfunction compared to subcutaneous adipose tissue (SAT). We hypothesized that inhibition of NADPH oxidase will reverse impaired Flow‐induced dilation (FID) in resistance arteries of VAT. Arterioles were dissected from VAT and SAT biopsies (BMI: 48±2, n=15) and cannulated for measurements of luminal diameters. Maximum dilations to papaverine (10−4 M) were determined. Production of hydrogen peroxide (H2O2) was measured by fluorescence microscopy. FID was reduced in VAT to 38±4% (p<0.01, at 60 cm H2O pressure gradient) compared to SAT (92±4%). Apocynin restored FID (73±5%) in VAT and had no effect in SAT. PEG‐catalase abolished the restored FID in the presence of apocynin. Incubation with apamin and tram‐34, blockers of small (SK)‐ and intermediate (IK)‐ conductance, Ca2+‐activated potassium channels, respectively, decreased this restored FID. Improved FID induced by the SK channel opener CyPPA was blocked by apamin. Flow‐ induced H2O2 generation was increased (1.7 fold) in the presence of apocynin compared to baseline and PEG‐catalase attenuated this increase. Taken together these data suggest that H2O2 and the activation of SK and IK channels contribute to the restored effect of apocynin on flow induced dilation in visceral fat during obesity. NIH (R01HL095701).