RESVERATROL IMPROVES MICROVASCULAR FUNCTION IN ADULTS WHO REPORTED ADVERSE CHILDHOOD EVENTS

INTRODUCTION Adversity early in life, referred to as adverse childhood events (ACEs), has been associated with the development of cardiovascular disease (CVDs) during adulthood. Microvascular dysfunction plays a pivotal role in the etiology of CVDs through a reduction in nitric oxide (NO)‐dependent vasodilation. Lower concentrations of sirtuin 1 (Sirt1), an NAD‐dependent protein that increases NO metabolism, have been described in multiple CVDs. PURPOSE This study sought to test the hypothesis that an acute dose of resveratrol (RES), a natural activator of Sirt1, will improve MVF in adults who reported ACEs. METHODS Ten adults (34 ± 3 yrs), with no evidence of overt CVD, participated in the study. Based on the ACE questionnaire, all participants had self‐reported an ACE score of 4 or greater. Two protocols were used to evaluate MVF using Laser Doppler flowmetry: 1) local thermal hyperemia (LTH), with a maximal plateau phase primarily mediated by NO, and 2) post‐occlusive reactive hyperemia (PORH), partly dependent on NO metabolism. MVF assessments were determined before and 90 min after an acute dose of either RES (500 mg) or Placebo (P), separated by at least 7 days and are expressed as cutaneous vascular conductance (CVC; cutaneous flux/mean arterial blood pressure). Maximal dilation capacity was evaluated through LTH. Skin resistance was also calculated for every individual and every treatment using Ohm's law and considered in all the statistical analysis. RESULTS No differences in resting CVC were observed between days (0.11 ± 0.08 vs. 0.11 ± 0.03 PU/mm Hg; p =0.297) or with the change from either treatment (ΔRES: −0.03 ± 0.03 vs. ΔP: −0.01 ± 0.01 PU/mm Hg; p =0.653). In addition, resveratrol significantly ( p =0.005) increased max LTH when compared with P (ΔRES: 0.12 ± 0.24 vs. ΔP: −0.06 ± 0.26, PU/mm Hg). Moreover, RES significantly ( p ≤0.001) prevented the decrease in PORH relative to the maximal dilation capacity when compared with placebo (ΔRES: −6.4 ± 1.4 vs. ΔP: −18.1 ± 17.8 %CVC max). In addition, the acute dose of RES increased concentrations of Sirt1 (RES: 1.3 ± 0.1 vs. ΔP: −0.4 ± 0.3 ng/ml; p =0.075) which was significantly associated with the max LTH response ( r =0.760; p=0.011). CONCLUSION These findings document an improvement in MVF after an acute oral dose of resveratrol in adults who have reported ACEs. Future studies are warranted to investigate the long term effects of resveratrol on MVF in adults who have reported ACEs. Support or Funding Information Supported in part by NIH/NHLBI P01HL069999 (JSP, RAH) and 16POST31080031 (PRM). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .