Endogenous nitric oxide and the pulmonary microvasculature in healthy sheep and during systemic inflammation.
Nitric oxide (NO) influences microvascular integrity. NO synthase inhibitors are regarded as therapeutic options, but their impact on the pulmonary microvasculature is not well defined. We studied the microvascular effects of the nonselective NO synthase inhibitor N(omega)-nitro L-arginine methylester (L-NAME) in healthy sheep and during systemic inflammation. Permeability analysis was performed in 30 adult ewes with chronic lung lymph fistulas and pulmonary venous occluders. Experiment 1: 20 sheep received Escherichia coli endotoxin (lipopolysaccharide, 10 ng/kg/min) for 32 h. After 24 h of endotoxemia, 10 sheep were given L-NAME (25 mg/kg), and 10 sheep received NaCl 0.9%. Experiment 2: six sheep were treated with L-NAME (25 mg/kg), and four animals received NaCl 0.9%. Endotoxin induced a phasic pulmonary microvascular response with early transiently increased endothelial permeability at 4 h and late normalization of microvascular integrity to large molecules after 24 h. At that time systemic vasodilation had occurred. L-NAME raised pulmonary artery pressure and pulmonary vascular resistance index without signs of increased permeability in either experiment. NO is involved in vascular tone in healthy sheep and during systemic inflammation, but it does not seem to play a role in the integrity of the pulmonary microvascular barrier function to large molecules.
Hinder
F
F
Department of Anesthesiology, The University of Texas Medical Branch, Galveston 77555-1091, USA.
Meyer
J
J
Booke
M
M
Ehardt
J S
JS
Salsbury
J R
JR
Traber
L D
LD
Traber
D L
DL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D019446:Endotoxemia / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008833:Microcirculation / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation; D012756:Sheep; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester