Vascular endothelial growth factor attenuates trauma-induced injury in rats.

Endothelial dysfunction and loss of nitric oxide (NO) is an integral part of the initiation and maintenance of the inflammatory process such as that occurring in traumatic shock, and is considered responsible for much of the trauma induced microvascular injury. We investigated the effects of a vascular endothelial growth factor (VEGF) in a rat model of traumatic shock. Pentobarbital-anaesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension and a 93% mortality rate with a mean survival time of 108+/-10 min in 14 rats. Accompanying these effects was a significant degree of endothelial dysfunction and a markedly elevated intestinal myeloperoxidase (MPO) activity. Treatment with 125 microg kg(-1) VEGF administered intravenously 18 h pre-trauma, increased survival rate to 67% (P<0.01), and prolonged survival time to 252+/-24 min in 12 rats (P<0.01). VEGF also significantly preserved the endothelium-dependent relaxation to ACh indicating a preservation of endothelium-derived NO. Our results indicate that endothelial dysfunction with its accompanying loss of NO plays an important role in tissue injury associated with trauma, and that preservation of NO is beneficial in traumatic shock. The mechanisms of the protective effect of VEGF in trauma involves preservation of eNOS function and diminished neutrophil accumulation resulting in reduced neutrophil-mediated tissue injury. British Journal of Pharmacology (2000) 129, 71 - 76