Time course of endothelial dysfunction and neutrophil adherence and infiltration during murine traumatic shock

Traumatic shock in rats has been shown to induce endothelial dysfunction, and to increase intestinal myeloperoxidase activity (MPO) indicative of neutrophil infiltration. To examine the time course of endothelial dysfunction and neutrophil adherence and infiltration, pentobarbital anesthetized rats, subjected to Noble-Collip drum trauma, were studied prior to and 15, 30, 60, 90, 120, 150, and 180 min following drum trauma. Superior mesenteric artery rings obtained from traumatized rats were tested for responsiveness to acetylcholine (ACh), a receptor-mediated endothelium-dependent vasodilator, and to NaNO2 an endothelium-independent vasodilator. ACh-induced relaxation was not impaired immediately after the induction of trauma (time 0). However, 15-30 min after trauma, responses to ACh were significantly depressed (p < .05) and were further reduced (p < .01) 90-180 min after trauma. No significant changes occurred in response to the direct vasodilator NaNO2 at any of the times studied, indicating no vascular smooth muscle injury. Moreover, the adherence of polymorphonuclear leukocytes (PMNs) to the post-traumatic mesenteric vascular endothelium also showed an increase that peaked 30 min post-trauma. Intestinal MPO activity, indicative of neutrophil infiltration, was characterized by a continuous and sustained increase from 30-180 min. Our findings suggest that endothelial dysfunction resulting in reduced NO release occurs in the early phase of murine traumatic shock, and that this phenomenon is followed by a time-dependent increase in adhesivity of neutrophils to the vascular endothelium leading to a progressive accumulation of PMNs in injured tissues (e.g., intestine).