Nitric oxide opposes phorbol ester-induced increases in microvascular permeability in dogs

In addition to its effects on vascular tone, nitric oxide (NO) has been suggested to function as a participant in fluid homeosta-sis affecting interactions between the endothelium and circu-lating inflammatory cells. The role of NO in the increased mi-crovascular permeability of acute lung injury, however, remains controversial. We investigated the hypothesis that NO opposes increases in pulmonary vascular permeability after phorbol my-ristate acetate administration, i.e., in a model of neutrophil-dependent acute lung injury. In anesthetized dogs, phorbol myristate acetate (10 mg/kg, i.v.) had no effect on pulmonary arterial pressure (Ppa) or extravascular lung water. After pre-treatment with the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (10 mg/kg, i.v.; 5 mg/kg/hr), an identical dose of phorbol myristate acetate resulted in a 20 6 8 mm Hg (P,.01