title: Nitric oxide and endothelial permeability.
abstract: Nitric oxide synthase inhibition reverses systemic vasodilation during sepsis but may increase endothelial permeability. To assess adverse effects on the pulmonary vasculature, 12 sheep were chronically instrumented with lung lymph fistulas and hydraulic pulmonary venous occluders. 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 Nomega-nitro-L-arginine methyl ester (L-NAME), and six received saline. All sheep developed a hyperdynamic circulatory response and elevated lymph flows by 24 h of lipopolysaccharide infusion. L-NAME reversed systemic vasodilation, increased pre- and postcapillary pulmonary 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-NAME 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 coefficients and elevated filtration coefficients without differences between groups. Reversal by L-NAME of the systemic vasodilation during endotoxemia was associated with high pulmonary vascular resistance without evidence of impaired pulmonary endothelial barrier function.
authors.affiliation: Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, der Westfälischen Wilhelms-Universität, Münster, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hinder
authors.forename: M
authors.initials: M
authors.lastname: Booke
authors.forename: L D
authors.initials: LD
authors.lastname: Traber
authors.forename: D L
authors.initials: DL
authors.lastname: Traber
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012756:Sheep; D012890:Sleep / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester