Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1–Dependent Uncoupling of Endothelial Nitric Oxide Synthase

• DOI: 10.1089/neu.2015.4340
• Publication Date: 2016-01-13T11:24:59Z
• Authors: Nuria Villalba; Adrian M. Sackheim; Ivette A. Nunez; David C. Hill-Eub...; Mark T. Nelson; George C. Wellman; Kalev Freeman
• Keywords: Endothelial Dysfunction

Endothelial dysfunction is a hallmark of many chronic diseases, including diabetes and long-term hypertension. We show that acute traumatic brain injury (TBI) leads to endothelial in rat mesenteric arteries. Endothelial-dependent dilation was greatly diminished 24 h after TBI because impaired nitric oxide (NO) production. The activity arginase, which competes with NO synthase (eNOS) for the common substrate l-arginine, were also significantly increased arteries, suggesting arginase-mediated depletion l-arginine underlies Consistent this, restoration by exogenous application or inhibition arginase recovered function. Moreover, evidence reactive oxygen species production, consequence starvation-dependent eNOS uncoupling, detected endothelium plasma. Collectively, our findings demonstrate remote vascular bed TBI, manifesting as endothelial-dependent vasodilation, activity, decreased generation NO, O2- conclude blood vessels have "molecular memory" neurotrauma, injury, functional changes cells; these effects are pertinent understanding systemic inflammatory response occurs even absence polytrauma.