Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.

Abstract

Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge-induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined whether the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n=14), moderate drinkers (MODs; n=10), and alcohol abstainers (ABs; n=12; mean age: 23.7±0.5years; and body mass index: 23.4±0.4kg/m2 ). Arteriolar flow-induced dilation (FID, pressure gradient: ∆10 to 100cm H2 O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. Before high pressure, FID at Δ60 and Δ100 cm H2 O pressure gradient in BDs was 14% lower and 18% lower, respectively, than ABs (p<0.05), while MODs and ABs had similar FID across all pressure gradients (p≥0.2). After high pressure, FID in BDs was further reduced by 10% (p<0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4 to 26% higher, p<0.005). In contrast, FID after high pressure did not change in MODs and ABs (p≥0.5). Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge-induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking.