NITRIC-OXIDE AND ENDOTHELIAL PERMEABILITY

Nitric oxide synthase inhibition reverses systemic vasodilation during sepsis but may increase endothelial permeability. To assess adverse e ffects on the pulmonary vasculature, 12 sheep were chronically instrum ented with lung lymph fistulas and hydraulic pulmonary venous occluder s. Escherichia coli endotoxin (lipopolysaccharide; 10 ng.kg(-1).min(-1 )) was continuously infused for 32 h. After 24 h, six animals received 25 mg/kg of N-omega-nitro-L-arginine methyl ester (L-NAME), and six r eceived saline. All sheep developed a hyperdynamic circulatory respons e and elevated lymph flows by 24 h of lipopolysaccharide infusion. L-N AME reversed systemic vasodilation, increased pre- and postcapillary p ulmonary vascular resistance index, pulmonary arterial pressure, and, transiently, effective pulmonary capillary pressure. Lung lymph flows were not different between groups at 24 h or thereafter. Calculated as changes from baseline, however, lung lymph flow was higher in the L-N AME group than in the control animals, with a trend toward lower lymph -to-plasma protein concentration ratio at 25 h. Permeability analysis at 32 h by the venous occlusion technique showed normal reflection coe fficients and elevated filtration coefficients without differences bet ween groups. Reversal by L-NAME of the systemic vasodilation during en dotoxemia was associated with high pulmonary vascular resistance witho ut evidence of impaired pulmonary endothelial barrier function.