H2O2 and NO contribute to Improved Flow‐Induced Dilations in Visceral and Subcutaneous Adipose Arterioles during Aerobic Exercise in Morbidly Obese Adults

Abstract

BACKGROUNDObesity is a major risk factor for cardiovascular disease. Our previous studies demonstrated that microvascular flow‐induced dilation (FID) is reduced in visceral adipose tissue (VAT) compared to subcutaneous AT (SAT) in morbidly obese subjects. Recent studies showed that VAT accumulation is more predictive of impaired vascular function than SAT. In the current study, we examine the differential effect of aerobic exercise (AE) training on improving the FID in SAT versus VAT microvessels in morbid obesity.METHODSWe obtained SAT and VAT biopsies from obese subjects undergoing bariatric surgery (n=6 and recruitment is ongoing; age: 35±3 yrs; BMI: 46±3 kg/m2; SBP: 114±6 mmHg; DBP: 80±7 mmHg) who were randomized to two groups (n=3 each): (1) AE training group (75% HRmax, 60 min/d, 2–3 d/wk, 4 wks) and (2) non‐exercising (control) group. Arterioles were isolated from SAT and VAT biopsies and cannulated for reactivity measurements in response to flow (pressure gradients of Δ10–Δ100 cmH2O) with and without the nitric oxide (NO) synthase (L‐NAME; 10−4 mol/L), PEGylated catalase (PEG‐Cat; 500 U/ml), or the superoxide dismutase (SOD) mimetic, Tempol (10−5 mol/L). NO and reactive oxygen species (ROS) generation were measured in the arterioles using NO detection dye and cell‐permeant ROS indicator (H2DCFDA).RESULTSFollowing training the AE group demonstrated reductions in BMI (−3%, p=0.03) and resting systolic BP (−4%, p=0.1). FID was higher in the AE than the control group across all pressure gradients (20–35% higher, p<0.05). The FID of VAT arterioles was reduced compared to SAT arterioles in both the AE and control groups. L‐NAME and PEG‐Cat reduced the FID (% of dilation at Δ60 pressure gradient) in the SAT arterioles in the AE group (L‐NAME: −18%, p=0.1; PEG‐Cat: −44%, p<0.001) and to a relatively lower extent in the control group (L‐NAME: −11%, p=0.1; PEG‐Cat: −29%, p=0.01). FID in the VAT arterioles was reduced in response to L‐NAME and PEG‐Cat (−14%, p=0.004; −38%, p=0.01, respectively) in the AE group however, no changes were detected in VAT arterioles from the control group. Tempol improved FID in the SAT and VAT arterioles; a higher magnitude of increase was noted in the control group (49%, p=0.01) compared to the AE group (16%, p=0.046) and in the VAT arterioles (49%, p=0.01) compared to the SAT arterioles (14%, p=0.02). Furthermore, the sensitivity of VAT arterioles to PEG‐Cat was induced by Tempol. PEG‐Cat reduced the FID in Tempol‐treated VAT arterioles by 47% and 35% (p<0.001) in the control and AE groups, respectively indicating that Tempol‐induced FID improvements in VAT arterioles may indicate an increased H2O2 production. Under flow conditions, NO‐fluorescence was greater and ROS generation lower in SAT arterioles compared to VAT arterioles and in the AE group compared to the control group.CONCLUSIONOur results suggest that 1) VAT arterioles display reduced vasodilator reactivity to flow compared to SAT arterioles and 2) AE training improves the FID in both SAT and VAT arterioles via NO and H2O2 dependent mechanisms.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.