Mary Szczurek

Binge Drinking Impairs Vascular Function in Young Adults

OBJECTIVES The aim of this study was to assess whether young binge drinkers (BD) have impaired macrovascular and microvascular function and cardiovascular disease risk factors compared with age-matched alcohol abstainers (A). BACKGROUND Binge drinking rates are highest on college campuses and among those age 18 to 25 years; however, macrovascular and microvascular endothelial function in young adults with histories of repeated binge drinking (≥ 5 standard drinks in 2 h in men, ≥ 4 standard drinks in 2 h in women) has not been investigated. METHODS Cardiovascular profiles, brachial artery endothelial-dependent flow-mediated dilation (FMD), and flow-independent nitroglycerin (NTG)-mediated dilation and vasoreactivity of resistance arteries (isolated from gluteal fat biopsies) were evaluated in A and BD. RESULTS Men and women (18 to 25 years of age; A, n = 17; BD, n = 19) were enrolled. In the BD group, past-month mean number of binge episodes was 6 ± 1, and the mean duration of binge drinking behavior was 4 ± 0.6 years. FMD and NTG-mediated dilation were significantly lower in the BD group (FMD: 8.4 ± 0.7%, p = 0.022; NTG-mediated dilation: 19.6 ± 2%, p = 0.009) than in the A group (FMD: 11 ± 0.7%; NTG-mediated dilation: 28.6 ± 2%). Acetylcholine-induced and sodium nitroprusside-induced dilation in resistance arteries was not significantly different between the A and BD groups. However, endothelin-1-induced constriction was significantly enhanced in the BD group compared with the A group (p = 0.032). No differences between groups were found in blood pressure, lipoproteins, and C-reactive protein. CONCLUSIONS Alterations in the macrocirculation and microcirculation may represent early clinical manifestations of cardiovascular risk in otherwise healthy young BD. This study has important clinical implications for screening young adults for a repeated history of binge drinking.

Hyperinsulinemia augments endothelin-1 protein expression and impairs vasodilation of human skeletal muscle arterioles.

Hyperinsulinemia is a hallmark of insulin resistance‐associated metabolic disorders. Under physiological conditions, insulin maintains a balance between nitric oxide (NO) and, the potent vasoconstrictor, endothelin‐1 (ET‐1). We tested the hypothesis that acute hyperinsulinemia will preferentially augment ET‐1 protein expression, disrupt the equilibrium between ET‐1 expression and endothelial NO synthase (eNOS) activation, and subsequently impair flow‐induced dilation (FID) in human skeletal muscle arterioles. Skeletal muscle biopsies were performed on 18 lean, healthy controls (LHCs) and 9 older, obese, type 2 diabetics (T2DM) before and during (120 min) a 40 mU/m2/min hyperinsulinemic‐euglycemic (5 mmol/L) clamp. Skeletal muscle protein was analyzed for ET‐1, eNOS, phosphorylated eNOS (p‐eNOS), and ET‐1 receptor type A (ETAR) and B (ETBR) expression. In a subset of T2DM (n = 6) and LHCs (n = 5), FID of isolated skeletal muscle arterioles was measured. Experimental hyperinsulinemia impaired FID (% of dilation at ∆60 pressure gradient) in LHCs (basal: 74.2 ± 2.0; insulin: 57.2 ± 3.3, P = 0.003) and T2DM (basal: 62.1 ± 3.6; insulin: 48.9 ± 3.6, P = 0.01). Hyperinsulinemia increased ET‐1 protein expression in LHCs (0.63 ± 0.04) and T2DM (0.86 ± 0.06) compared to basal conditions (LHCs: 0.44 ± 0.05, P = 0.007; T2DM: 0.69 ± 0.06, P = 0.02). Insulin decreased p‐eNOS (serine 1177) only in T2DM (basal: 0.28 ± 0.07; insulin: 0.17 ± 0.04, P = 0.03). In LHCs, hyperinsulinemia disturbed the balance between ETAR and ETBR receptors known to mediate vasoconstrictor and vasodilator actions of ET‐1, respectively. Moreover, hyperinsulinemia markedly impaired plasma NO concentration in both LHCs and T2DM. These data suggest that hyperinsulinemia disturbs the vasomotor balance in human skeletal muscle favoring vasoconstrictive pathways, eventually impairing arteriolar vasodilation.

Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training

Objective: Acute strenuous physical exertion impairs arterial function in sedentary adults. We investigated the effects of 8 weeks of regular aerobic exercise training on acute physical exertion-induced arterial dysfunction in sedentary, overweight, and obese adults. Methods: Twenty-five overweight and obese adults (BMI 30.5 ± 7.2 years) were assigned to 8 weeks of aerobic training or to a control group. Brachial artery flow-mediated dilation (FMD) was assessed before and after acute leg press exercise at weeks 0 and 8. Gluteal adipose biopsies were performed at rest and post acute leg press to measure microvessel FMD with and without nitric oxide synthase inhibition via LNG-nitroarginine methyl ester or hydrogen peroxide (H2O2) scavenging with Catalase. Microvessel nitric oxide and H2O2 production were assessed via fluorescence microscopy. Results: Brachial artery dilation was reduced post acute leg press at week 0 in the aerobic exercise and control groups, but was preserved in the aerobic-exercise group post acute leg press at week 8 (P < 0.05). Post acute leg press microvessel FMD was preserved in the aerobic exercise group but impaired in the control group at week 8 (P < 0.05). Preserved dilation in the aerobic exercise group was more sensitive to H2O2 scavenging than inhibition of nitric oxide, and post acute leg press microvessel H2O2 production was increased compared with at rest (P < 0.05). Conclusion: Aerobic exercise prevents acute exertion-induced arterial dysfunction in overweight and obese adults via a phenotypic switch from nitric oxide-mediated dilation at rest to a predominately H2O2-mediated dilation after acute physical exertion.

Reduced Flow‐and Acetylcholine‐Induced Dilations in Visceral Compared to Subcutaneous Adipose Arterioles in Human Morbid Obesity

The hypothesis of this study was that microvascular FID and AChID is impaired in visceral (VAT) compared to SAT arterioles in morbidly obese women. An Additional aim was to determine the mechanisms contributing to FID and AChID in VAT and SAT arterioles.