A dominant feature of post-traumatic/septic lung injury is pulmonary hypertension. Utilizing a rat model of acute lung injury, the mechanisms of altered pulmonary arterial smooth muscle tone will be interrogated. The purpose of these investigations is: 1) To determine the effects of TNF induced, neutrophil mediated dysfunction on pulmonary vasorelaxation; 2) To determine if an anti-inflammatory cytokine, IL-11, ameliorates lung injury by the prevention of lung neutrophil accumulation, alveolar macrophage TNF production, and endothelium-dependent/endothelium-independent vasomotor dysfunction; 3) To elucidate mechanisms through which proinflammatory cytokines exert deleterious effects or anti-inflammatory cytokines exert beneficial effects on pulmonary vasomotor function which may allow development of focused therapies directed to posttraumatic lung injury.

R03HD036256

1998-05-01

2001-01-30