期刊
JOURNAL OF NEUROTRAUMA
卷 34, 期 1, 页码 192-203出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2015.4340
关键词
in vitro studies; oxidative stress; traumatic brain injury; vascular injury; vascular reactivity
资金
- Totman Medical Research Trust
- Fondation Leducq
- National Institutes of Health [P20-RR-16435, P01-HL-095488, UM1-HL-120877-01, R01-HL-044455, R01-HL-098243, R37-DK-053832, P30-RR-032135-02, P30-GM-103498-02, K08-GM-098795-01, R01-HL-121706-01]
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 O-2-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.
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