Binge but Not Moderate Drinking Impairs Microvascular Flow Induced Dilation Following High Pressure in Young Adults

Abstract

Binge drinking or heavy‐episodic drinking is an emerging cardiovascular risk factor and is prevalent among young adults. On the other hand, moderate drinking may also increase cardiovascular risk. We previously demonstrated that flow‐induced dilation (FID) is reduced in young adult binge drinkers compared to abstainers. However, little is known about alteration associated with alcohol use in the vascular response to environmental stress (e.g. high pressure) or vascular function in moderate drinkers. Therefore, we sought to examine FID following high pressure in binge drinkers, moderate drinkers, and abstainers. In addition, we used tetrahydrobiopterin (BH4) to investigate the possible underlying mechanism. We isolated arterioles from gluteal subcutaneous adipose biopsies from 33 young adults (binge drinkers: n=12, moderate drinkers: n=11, and abstainers: n=10; age: 24±1 yrs and body mass index: 23.6±0.4 kg/m2; mean±SE). Arterioles were cannulated and pressurized (60 cmH2O) in an organ perfusion chamber. Lumen diameters were measured before and during responses to flow (pressure gradients of Δ10‐Δ100 cmH2O) prior to and following 1‐hour high intraluminal pressure (150 cmH2O) in the presence or absence of BH4 (10−5 M). Prior to high pressure, we found that moderate drinkers had similar FID across all pressure gradients as abstainers (P>0.1). At Δ100 cmH2O pressure gradient, both moderate drinkers and abstainers had higher % vasodilation than binge drinkers (13% higher, P=0.0047 and 20% higher, P<0.0005 respectively). This impairment in binge drinkers was restored by BH4 (+12%, P=0.02 vs. absence of BH4 and P>0.06 vs. moderate drinkers and abstainers). Following high pressure, FID was reduced only in binge drinkers (3–17% lower, P=0.005 vs. prior to high pressure) while the vasodilatory response to flow was maintained in moderate drinkers and abstainers (P>0.4 vs. prior to high pressure). BH4 ameliorated the impaired FID following high pressure across all pressure gradients in binge drinkers (+4–26%, P<0.05 vs. absence of BH4). In conclusion, arterioles from young adults who abstain or who drink moderately show maintained FID following exposure to elevated vascular pressure. The impaired FID associated with binge drinking can be further reduced by high pressure and reversed by treatment with BH4, suggesting endothelial nitric oxide synthase uncoupling in endothelial dysfunction induced by high pressure in binge drinkers.Support or Funding InformationNIH R01 HL095701 and R21 AA024535This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.