Mitochondrial reactive oxygen species contribute to impaired flow‐induced dilation in visceral but not subcutaneous adipose tissue resistance arteries in human obesity

Abstract

Microvascular dysfunction contributes to cardiovascular disease risk. Previous studies indicate that flow‐induced dilation (FID) is impaired in resistance arteries from visceral adipose tissue (VAT) compared to subcutaneous adipose tissue (SAT), in obese subjects. We hypothesized that mitochondrial reactive oxygen species contribute to altered mechanisms of FID in VAT. Resistance arteries (RAs) were dissected from VAT and SAT biopsies obtained from obese subjects during bariatric surgery (n=17 BMI: 48±2). Intraluminal diameters were measured via videomicroscopy before and during flow (pressure gradient 10 to 100 cmH2O) in the presence and absence of Tempol (100μM), PEG‐catalase (PEG‐CAT; 500 U/ml), L‐NAME 100 μM), and Rotenone (50 μM). Fluorescent quantification of flow‐induced H2O2 and nitric oxide (NO) production was also determined. Rotenone improved FID (77±8% vs. 39±4% P<.001) and increased generation of H2O2 and NO in RAs of VAT. There was no effect of Rotenone on FID or H2O2 production in SAT. The addition of PEG‐CAT or L‐NAME to rotenone eliminated the improved FID in VAT. Tempol improved FID in RAs of both VAT and SAT, but was abolished by PEG‐CAT. Taken together these data suggest that 1) mitochondrial ROS contribute to impaired FID in VAT and 2) H2O2 and NO contribute to the restored dilation induced by rotenone and Tempol in visceral adipose during obesity.