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Traumatic Brain Injury Causes Endothelial Dysfunction in the Systemic Microcirculation through Arginase-1-Dependent Uncoupling of Endothelial Nitric Oxide Synthase.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Villalba, Nuria Sackheim, Adrian M. Nunez, Ivette Ariela Hill-Eubanks, David C. Nelson, Mark T. Wellman, George C. Freeman, Kalev |
| Copyright Year | 2017 |
| Abstract | 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 dysfunction in rat mesenteric arteries. Endothelial-dependent dilation was greatly diminished 24 h after TBI because of impaired nitric oxide (NO) production. The activity of arginase, which competes with endothelial NO synthase (eNOS) for the common substrate l-arginine, were also significantly increased in arteries, suggesting that arginase-mediated depletion of l-arginine underlies diminished NO production. Consistent with this, substrate restoration by exogenous application of l-arginine or inhibition of arginase recovered endothelial function. Moreover, evidence for increased reactive oxygen species production, a consequence of l-arginine starvation-dependent eNOS uncoupling, was detected in endothelium and plasma. Collectively, our findings demonstrate endothelial dysfunction in a remote vascular bed after TBI, manifesting as impaired endothelial-dependent vasodilation, with increased arginase activity, decreased generation of NO, and increased O2- production. We conclude that blood vessels have a "molecular memory" of neurotrauma, 24 h after injury, because of functional changes in vascular endothelial cells; these effects are pertinent to understanding the systemic inflammatory response that occurs after TBI even in the absence of polytrauma. |
| Starting Page | 192 |
| Ending Page | 203 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| DOI | 10.1089/neu.2015.4340 |
| PubMed reference number | 26757855 |
| Journal | Medline |
| Volume Number | 34 |
| Issue Number | 1 |
| Alternate Webpage(s) | https://www.research.manchester.ac.uk/portal/files/50445432/BA2B0B13.pdf |
| Alternate Webpage(s) | https://doi.org/10.1089/neu.2015.4340 |
| Journal | Journal of neurotrauma |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
