Organ sites of lipopolysaccharide-induced nitric oxide production in the anesthetized rat.
The objective of this research was to determine the amount and timing of nitric oxide (NO, nitrogen monoxide) gas produced by the lungs, intestinal mucosa, and organ surfaces facing the peritoneal cavity after iv injection of a bacterial toxin, lipopolysaccharide (LPS). Some of the deleterious effects of LPS on organ function have been attributed to NO or strong oxidants formed locally from NO. Medical-grade air was used as an inspiratory air source (50 strokes/min x 3 ml/stroke) or was pumped through the ileal lumen or peritoneal cavity (20 strokes/min x 3 ml/stroke). The air was collected at intervals of 15-30 min for 3 h after LPS and analyzed for authentic NO gas by chemiluminescence. LPS (5 mg/kg) or saline was injected iv. Sodium nitroprusside (SNP) was injected to determine the appearance of its NO released into the perfused compartments. Blood pressure, plasma nitrate plus nitrite (NO(x)), and total plasma leukocytes were measured as other manifestations of LPS effects. NO began to increase in the pulmonary expired air 90 min after LPS and continued to increase for the remainder of the experiment. The final pulmonary post-LPS [NO] was about 20-fold greater than the [NO] before LPS. LPS had no effect on intraluminal or intraperitoneal [NO]. The saline injection had no effect on [NO] in any compartment. SNP injection increased NO entry into all three air-perfused compartments. Thus, NO from an exogenous tissue source was not prevented from being detected. Blood pressure was decreased by LPS only during the pulmonary perfusion. There were no significant effects of LPS on leukocytes or plasma NO(x). LPS decreased blood pressure and leukocytes and increased plasma NO(x) when air perfusion was not done. It was concluded that different organs can produce LPS-induced NO at markedly different rates and times. However, some aspect of the experimental technique of air perfusion could alter the effects of LPS.
Mailman
D
D
Biology and Biochemistry Department, University of Houston, Houston, Texas 77204, USA. dmailman@uh.edu
Guntuku
S
S
Bhuiyan
M B
MB
Murad
F
F
D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D007022:Hypotension / Q000503:physiopathology; D007082:Ileum; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008163:Luminescent Measurements; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D010477:Perfusion; D010529:Peritoneal Cavity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009599:Nitroprusside; D009569:Nitric Oxide